Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Institute of Mental Health (NIMH)
Funding Opportunity Title	Gut-Microbiome-Brain Interactions and Mental Health (R21/R33)
Activity Code	R21/R33 Phased Innovation Award
Announcement Type	New
Related Notices	September 11, 2014 - This RFA has been reissued as RFA-MH-15-850. October 18, 2013 - See Notice NOT-OD-14-003. Guidance on Resumption of NIH Extramural Activities Following the Recent Lapse in Appropriations. August 21, 2013: Removed reference to ASSIST in section IV.3, since ASSIST is currently only available for multi-project applications. May 30, 2013 (NOT-OD-13-074) - NIH to Require Use of Updated Electronic Application Forms for Due Dates on or after September 25, 2013. Forms-C applications are required for due dates on or after September 25, 2013.
Funding Opportunity Announcement (FOA) Number	RFA-MH-14-080
Companion Funding Opportunity	None
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.242
Funding Opportunity Purpose	This Funding Opportunity Announcement (FOA) encourages research grant applications from institutions/organizations to investigate mechanisms by which the gut microbiome modulates the development and function of brain circuits that subserve behavioral functions of direct relevance to the mission of the NIMH. Because initial colonization of the gut by microbiota occurs early in life and may influence the subsequent development and modifiability of the central nervous system, developmental studies are of particular interest. Applicants may propose to use wild-type, gnotobiotic, or specific pathogen-free model organisms and/or human cohorts. With this FOA, the NIMH encourages investigator teams to initiate hypothesis-driven research in this cross-cutting research area and to identify promising mechanistic leads for future basic and translational research that will advance the mission of the NIMH.

Posted Date	March 8, 2013
Open Date (Earliest Submission Date)	September 10, 2013
Letter of Intent Due Date(s)	September 10, 2013
Application Due Date(s)	(Extended to November 1, 2013 per NOT-OD-14-003), Originally October 10, 2013, by 5:00 PM local time of applicant organization. Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
AIDS Application Due Date(s)	Not Applicable
Scientific Merit Review	February 2014
Advisory Council Review	May 2014
Earliest Start Date	July 2014
Expiration Date	(Extended to November 2, 2013 per NOT-OD-14-003), Originally October 11, 2013
Due Dates for E.O. 12372	Not Applicable

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 over-arching goal of this Funding Opportunity Announcement (FOA) is to encourage multidisciplinary teams of investigators to initiate hypothesis-driven research that will begin to investigate mechanisms by which gut microbiota may influence pre- and postnatal neurodevelopment as well as genes, signaling cascades, synaptic plasticity, and brain circuits that subserve domains of function of direct relevance to mental health and mental disorders.

The Human Microbiome Project (HMP) of the NIH Common Fund was established in 2007 to generate resources that would enable characterization of the human microbiota and analysis of their role in human health and disease. To date, researchers have characterized the microbial communities found at five different sites on the human body, including nasal passages, oral cavities, skin, gastrointestinal tract, and urogenital tract, and have begun to analyze them. Metagenomics tools and other technologies developed through the HMP are being applied to assess microbiota at the genetic level; such tools can be applied in future research to address functional consequences of host-microbiome interactions as they may shape brain function and behavior. With this FOA, the NIMH seeks to capitalize on the momentum and foundational science of the HMP and related international efforts and to encourage novel scientific studies of the gut microbiome-brain axis to establish its role in mental health and mental disorders.

The human gastrointestinal tract harbors over 1x1013 different microbes, a number well in excess of the number of human eukaryotic cells. The relationship between the gut microbiome and the brain is believed to be bi-directional, i.e., gut microbiota may modulate brain function and the brain may alter the gut microbiome, e.g., by changing gastrointestinal motility and intestinal permeability. Of particular interest for this FOA, however, is communication from the microbiota in the gut to the brain. Studies conducted over the last decade in rodents, in the aggregate, suggest that gut microbiota can modulate brain development, neurotransmitter systems, canonical signaling pathways, synaptic related proteins and behavior. The microbiome may also be an important link between our genes and exposure to environmental factors that influence susceptibility to psychiatric disorders. Immune, neural, and/or enteroendocrine mechanisms as well as soluble factors and/or metabolites of commensal bacteria may enable gut microbiota to influence the brain and to influence its development in utero, during and after birth. However, the specific pathways and mechanisms underlying communication between the gut microbiome and the brain are poorly understood. An enhanced understanding of mechanisms underlying gut microbiome-brain interactions may thus provide novel insights into neurodevelopment, brain function, and behavior.

By virtue of the cross-disciplinary focus of this FOA, partnerships between investigators with expertise in neuroscience and in microbiology and/or immunology are strongly encouraged.

The FOA encourages exploratory development followed by hypothesis-driven research that will investigate mechanisms by which the gut microbiota influences pre- and postnatal neurodevelopment as well as genes, signaling cascades, synaptic plasticity, and brain circuits related to behavioral domains directly relevant to the mission of NIMH (see NIMH Strategic Plan and Strategic Research Priorities). Such efforts are expected to increase our knowledge of microbiome-brain interactions, enhance our mechanistic understanding of the brain and behavior, and inform our understanding of the etiology of psychiatric disorders.

Although the gut microbiome includes viruses, protozoa, archaea, and fungi, it is dominated by bacteria. For this reason, this FOA is limited to applications that propose to investigate the bacterial component of the gut microbiota.

Applicants may propose to use wild-type, gnotobiotic, or specific pathogen-free model organisms and/or human cohorts. The services of the National Gnotobiotic Rodent Resource Center may be relevant to potential applicants.

Examples of research topics of interest include, but are not limited to, the following:

• Cellular, molecular and physiological studies to identify mechanisms by which the gut microbiota modulates neural circuits that subserve specific domains of function such as working memory, emotion regulation, social processes, and higher-level executive functions.
• Mechanistic studies of the role of the microbiome-gut-brain axis in pre- and postnatal brain development.
• Mechanistic studies mapping developmental trajectories of the effects of the gut microbiota on neural systems with the goal to identify aberrant developmental patterns in neural circuits that subserve specific domains of function such as higher-order cognitive and emotional processes.
• Studies of sex differences in effects of the gut microbiota on the modifiability of neural and circuit function across the lifespan.
• Studies examining the mechanisms by which perturbation of the maternal gut microbiota alters prenatal brain development and subsequent brain function and behavior.
• Studies examining the mechanisms by which perturbations (e.g., via the maternal vaginal microbiota) of the offspring's gut microbiota affect brain function and behavior.

Responsive applications will include hypothesis-driven, mechanistic studies that focus on pathways of communication from the bacterial component of the gut microbiota to the brain with outcome measures aimed at defining the neural functions that underlie complex behaviors related to mood, cognition, and social function.

Because such studies may require several areas of expertise, applicants are encouraged to include multiple PDs/PIs or collaborators on the application.

• Applications focused on psychiatric co-morbidities (e.g., irritable bowel syndrome, inflammatory bowel disease, and sleep and circadian rhythm disorders), effects of illicit substances, prescription drugs, dietary supplements, or environmental toxicants will not be considered responsive to this FOA and will not be reviewed.
• Applications focused on nutrition, ingestive, or metabolic functions will not be considered responsive to the FOA and will not be reviewed.
• Applications focused on HIV-AIDS will not be considered responsive to this FOA and will not be reviewed.

NIH understands and accepts that early stage, high-risk/high-impact applications that are responsive to this funding opportunity will be much riskier than for most other funding opportunities.

Applicants are strongly encouraged to consult with the Scientific/Research Contact(s) to discuss potential research projects prior to submitting an application.

This FOA uses the R21/R33 Phased Innovation Award mechanism. The R21 phase will support initial, exploratory development and characterization that is needed to establish feasibility of the mechanistic studies. The R33 phase will likely support hypothesis-driven, mechanistic studies. Transition from the R21 to the R33 phase is contingent upon successful completion of the proposed milestones for research progress. These milestones must be included in the Research Strategy section of the application and will be evaluated as part of the scientific and technical merit of the R21/R33 application.

Funding Instrument	Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.
Application Types Allowed	New The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	NIMH intends to commit approximately $2,000,000 in FY 2014 to fund six to nine awards.
Award Budget	Direct costs are limited to a maximum of $175,000 per year for the R21 phase and less than $500,000 per year for the R33 phase. Although treated as direct costs, consortium F&A does not apply toward any direct cost cap. The R21 and R33 cannot be funded in the same fiscal year.
Award Project Period	The total project period for a combined R21/R33 application may not exceed 5 years, with no more than three years for either the R21 phase or the R33 phase.

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 and should work with their organizational officials to either create a new account or to affiliate an existing account with the applicant organization’s eRA Commons account. 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.

NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for 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, 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.

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:

Nancy L Desmond, PhD
Division of Neuroscience and Basic Behavioral Science
National Institute of Mental Health
6001 Executive Boulevard, Room 7197, MSC 9645
Bethesda, MD 20892-9645
Rockville, MD 20852 (for express/courier service)
Telephone: 301-443-3107
Email: ndesmond@nih.gov

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

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

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

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

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

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

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

• The R21/R33 Phased Innovation Award application must be submitted as a single application with one Research & Related Budget component.
• Budget Justification: For each budget year, indicate if the requested budget is for the R21 phase or the R33 phase.
• The R21 and R33 cannot be funded in the same fiscal year.

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:

• The R21/R33 Phased Innovation Award application must be submitted as a single application with one PHS398 Cover Page Supplement component.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Specific Instructions for Preparing a Combined R21/R33 Phased Innovation Award Application

Within the Research Strategy, applicants should describe both the R21 phase and the R33 phase, including the milestones and timeline.

The milestones and timeline proposed in the application should be well described, quantifiable, and scientifically justified to allow Program Staff to assess progress toward the proposed Specific Aims during both the R21 and the R33 phases. The milestones will be considered in evaluating the approach proposed by the investigator. A discussion of the milestones relative to the progress of the R21 phase and the implications of successful completion of the milestones for the R33 phase should be included. Applications lacking this information, as determined by NIH staff, will not be reviewed. Clarity and completeness of the application with regard to specific goals and feasibility milestones are critical.

Specific Aims: Under each header, state the specific objectives of the research and development effort, including any technical questions you will try to answer to determine the feasibility of the proposed approach. Since the goal of the R21 phase of this FOA is to conduct pilot, exploratory studies that provide proof of principle for the feasibility of the proposed R33 phase research, hypothesis testing, per se, may not be applicable during the R21 phase.

Research Strategy: As part of the Research Strategy, applications are required to include a project timeline with specific, yearly milestones that can be used to facilitate the evaluation of progress, including the transition from the R21 phase to the R33 phase. Upon achieving agreed-upon milestones for the R21 phase, awardees may be eligible to receive up to three additional years of support in the R33 phase. See Section IV - Application and Submission Information and Section V.2 - Review and Selection Process, for additional information regarding the proposed timeline and milestones.

Innovation: Follow the instructions in the SF424 Application Guide. 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: Follow the instructions in the SF424 Application Guide. 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.

Milestones and Timeline (limit, one half page): As part of the Research Strategy, provide a timeline with specific milestones for accomplishing the proposed research, including specific milestones for progression from the R21 phase to the R33 phase. Indicate when it is anticipated that essential components of the project (e.g., optimization of protocols, generation of reagents, critical experiments to verify the hypothesis, validation of novel tools or techniques) will be completed. The proposed timeline should be clearly delineated and should appear as the last element of the Research Strategy section.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modification:

• The Data and Resource Sharing section of the application should include details related to sharing reagents, tools, protocols, and data generated as a result of this project (see http://grants.nih.gov/grants/policy/data_sharing/). For the last category, applicants should describe who will have access to data, and how, when, and where data would be accessed.

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

Foreign (non-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.

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 by the Center for Scientific Review and responsiveness by NIMH, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.

In order to expedite review, applicants are requested to notify the NIMH Referral Office by email at NIMHReferral@mail.nih.gov when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

Prior to funding an application, the Program Officer will contact the applicant to discuss the proposed milestones and any changes suggested by the review panel as indicated in the Summary Statement. The Program Officer and the applicant will discuss and agree on a final set of milestones. These will be the basis for judging the success of the R21 work.

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 grant supports exploratory/developmental investigation of novel scientific ideas or new model systems, tools, or technologies that have the potential for significant impact on biomedical or biobehavioral research. An R21/R33 grant application need not have extensive background material or preliminary information. Accordingly, reviewers will focus their evaluation on the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Preliminary data are not required for R21/R33 applications; however, they may be included if available.

For the R21/R33 Phased Innovation Award application, the initial review group will evaluate the specific goals for each phase and the feasibility milestones that would justify expansion to the R33 phase. A single overall impact/priority score will be assigned to each discussed application.

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? If successful, will the project advance our mechanistic understanding of the role of the gut microbiome in neurodevelopment, brain function and behavior?

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?

Innovation

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

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?

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

Environment

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

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

Milestones and Timeline

Are the proposed milestones and timeline well-defined, feasible and appropriate for judging the success of the R21 phase of the application? Are the proposed milestones appropriate for determining whether the R33 phase should be awarded? Do the milestones and timeline establish feasibility for all aspects of the proposed R33 work? Is it clear how the R33 phase will develop once the R21 milestones are achieved?

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Children

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

Vertebrate Animals

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

Biohazards

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

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

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.

Applications from Foreign Organizations

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

Select Agent Research

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

Resource Sharing Plans

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

Budget and Period of Support

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

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s), convened by the NIMH, 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 Mental Health Council. 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 the DUNS, SAM Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

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

Cooperative Agreement Terms and Conditions of Award

Not Applicable

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

For funded applications, the Project Director/Principal Investigator (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, on program priorities, and on 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)

Phone: 301-402-7469 or 866-504-9552 (Toll Free)

Web ticketing system: https://public.era.nih.gov/commonshelp
TTY: 301-451-5939
Email: commons@od.nih.gov

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

Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-710-0267
TTY 301-451-5936
Email: GrantsInfo@nih.gov

Nancy L Desmond, PhD
National Institute of Mental Health (NIMH)
Telephone: 301-443-3107
Email: ndesmond@nih.gov

David Armstrong, PhD
National Institute of Mental Health (NIMH)
Telephone: 301-443-3534
Email: amstrda@mail.nih.gov

Terri Jarosik
National Institute of Mental Health (NIMH)
Telephone: (301) 443-3858
Email: tjarosik@mail.nih.gov

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

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.