Part 1. Overview Information

Key Dates

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 2. Full Text of Announcement

Section I. Funding Opportunity Description

Background:

Epidemiological studies have shown that psychiatric disorders, constitute a significant public health burden across diverse populations worldwide. These mental disorders are characterized by marked genetic heterogeneity, with both common and rare variation contributing to the complex phenotypic outcomes. For reasons such as population homogeneity and ease of ascertainment, most genome-wide genetic studies to date have mainly focused on cohorts of European-ancestry, however, no single population is sufficient to fully uncover the variants underlying neuropsychiatric diseases in all populations. The absence of diverse ancestries in genome-wide association studies has therefore negatively impacted their ability to illuminate the full genetic architecture of complex neuropsychiatric traits. Populations with different ancestral origins vary in terms of allele frequencies, biological adaptations, and other properties that affect the detectability and importance of risk variants. Lack of ancestrally diverse genome-wide data can lead to the misidentification of causal variants due to cryptic population stratification or simply overlooking a causal variant altogether, since rare variants are likely to be more recent in origin and more geographically localized. Further inclusion of global populations of non-European ancestry in genome-wide studies is necessary for comprehensive gene discovery efforts to identify true disease causal variants. Native populations of non-European origin will allow for fine-mapping of genetic loci through population differences in variant frequencies, as well as testing of both the effects of more recent rare alleles within those populations and whether ancient functional alleles that are not present in European populations confer risk of severe mental illness when coupled with these more recent alleles of severe effect (e.g. compound heterozygosity, digenic inheritance, or oligogenic inheritance). Furthermore, diverse representation of global ancestral populations in genetic studies will advance the goal of global mental health equity.

Research Objectives:

This Funding Opportunity Announcement (FOA) seeks applications proposing coordinated efforts to accelerate gene discovery for psychiatric disorders in cohorts of non European ancestry to advance the important goal of global mental health equity. Projects should apply cutting-edge genome-wide approaches and incorporate clinical assessments, including structured clinical interviews (e.g., Structured Clinical Interview for DSM [SCID], Diagnostic Interview for Genetics Studies [DIGS], Family Interview for Genetic Studies [FIGS]), and other phenotypic data such as dimensional measures (e.g., as represented in PhenX Toolkit, NIH Toolbox, RDoC). Recruitment of new subjects or re-contact of existing subjects for the purpose of collecting new biospecimens or obtaining more complete clinical data is permitted. Projects are also encouraged to leverage existing data resources (e.g., medical records, genetic data, or phenotypic data). Projects are encouraged to coordinate with other ongoing NIH and NIMH consortia efforts in psychiatry and genetics worldwide and to leverage existing infrastructure and collaborative networks where research-grade psychiatric diagnostic assessments are performed and that are primed to conduct genomic analysis in non European ancestral populations (i.e. projects are encouraged to coordinate with with any nearby NIMH Global Health Hubs). Projects are strongly encouraged to form collaborative teams that include researchers from the countries where these populations will be recruited.

Specifically, this FOA seeks to support the genetic and clinical characterization of subjects with highly-heritable severe mental illness (e.g., schizophrenia, autism and bipolar disorder) in global populations of African ancestry on the African continent for the purpose of enhancing efforts to fine-map genetic risk loci across the allelic spectrum. Examples of such studies include, but are not limited to:

Broad sharing of biomaterials, genetic data, and phenotypic data with the NIMH Repository and Genomics Resource (NRGR) and other NIH databases (e.g., dbGaP) for use by the global scientific community is expected for all projects supported through this initiative as permitted by national and local policies and regulations (NOT-MH-19-033).

This FOA is one of several FOAs participating in a program called Ending Disparities in Mental Health (EDIfy-MH). The EDIfy-MH program stimulates and encourages mental health disparities research that spans the NIMH strategic research priorities, from basic science to services research, and across the lifespan in the United States and worldwide. Globally, EDIfy-MH encourages research that includes, but is not limited to, the following: low- and middle- income countries, 2 communities in low-resource settings, individuals living in rural areas, socioeconomically disadvantaged persons, or any other subgroups with documented disparities in prevalence of mental illnesses, mental illness trajectories, access to preventive and treatment intervention services, and quality and outcomes of mental health care.

Globally, EDIfy-MH encourages research that includes, but is not limited to, the following: low- and middle- income countries, 2 communities in low-resource settings, individuals living in rural areas, socioeconomically disadvantaged persons, or any other subgroups with documented disparities in prevalence of mental illnesses, mental illness trajectories, access to preventive and treatment intervention services, and quality and outcomes of mental health care.

Organization and Management of the Global Mental Health Genetics Network

Protection of Human Subjects: Applications with data collection plans that involve multiple respondent groups (e.g., clients/patients, therapists/providers, supervisors, and administrators) should address provisions for human subjects protections and consenting procedures for all participant groups accordingly. The NIMH has published updated policies and guidance for investigators regarding human research protections and clinical research data and safety monitoring (NOT-MH-19-027). The application’s Protection of Human Subjects section and data and safety monitoring plans should reflect the policies and guidance in this notice. Plans for the protection of research subjects and data and safety monitoring will be reviewed by the NIMH for consistency with NIMH and NIH policies and federal regulations.

The human subjects section of each member of the collaborative must be site-specific, reflecting the relevant conditions and situations for that institution and application.

Section II. Award Information

Section III. Eligibility Information

1. Eligible Applicants

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

• 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)

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.

Multiple PDs/PIs are allowed on any single application. Because the FOA already supports a team approach between groups of experts across sites and collaborating applications, the designation of multiple PDs/PIs on a single application may be less likely to apply. PD(s)/PI(s) from each linked application should not be designated as multiple PDs/PIs on each application of a collaborative set.

2. Cost Sharing

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

3. Additional Information on Eligibility

Number of Applications

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)

This FOA only accepts applications that are part of a collaborative set of multiple applications. A set must contain at least 2 applications.

Section IV. Application and Submission Information

1. Requesting an Application Package

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.

2. Content and Form of Application Submission

Letter of Intent

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]

Descriptive Title of Applicant's Project: To allow NIH to identify a group of applications as a related set of collaborative applications, the titles for each application in the set must have the following format: a 1/N indicator + Identical Title (e.g., 1/3 , where the 1/3 means this is site 1 of 3 sites in the set. The other sites will be labeled 2/3, etc.) Titles may not exceed 200 characters in length, including the tag, e.g., 1/3, at the beginning of the title.

Cover Letter Attachment: The Cover Letter is one pdf file only. The following collaborative information is required in the Cover Letter: a listing of all the applications that are a part of the set of collaborative applications being submitted, including for each: 1) the PD/PI(s) name(s), 2) the Title (including the tag, e.g., 1/3 ), and 3) the Applicant Institution. Each site should submit an identical listing.

Facilities and Other Resources:

Each application in a set of linked collaborative U01s must describe the facilities and resources available for that application. It is expected that this section of the application will be different in each of the linked applications. Applicants should especially focus on the unique resources at their institution and any sub-contracts which lend themselves to the completion of the project.

Other Attachments: The following items must be included as other attachments.

1. Project Management Plan

Each collaborative application must provide an identical Project Management Plan across sites, submitted as a pdf attachment with the title "Project Management Plan."

Provide a plan detailing the measures that will be taken to ensure cross-disciplinary communication and integration across the team (i.e., the collaborating laboratories) and addressing the division of labor across the team. The Project Management Plan must provide a detailed description of how different elements of the project would operate in a synergistic and integrated manner, including a data coordination plan. The following guidelines and framework must be followed in developing this plan:

• Describe how scientific research procedures, especially phenotyping protocols, will be standardized across different laboratories and elements within a project, including training and procedures to assure reliability and quality control.
• Describe how the overall managerial and administrative responsibilities will be divided in a team (i.e., which laboratory will coordinate various parts of the project and which will be responsible for overall coordination).
• Describe the plans for project data coordination, including standards and integration, and plans for ensuring comprehensive transparency of data reporting/sharing as appropriate and consistent with achieving the goals of the program.
• Include plans for ensuring: replication, comprehensive transparency of data and rapid reporting/sharing of data to the network members, and rapid access to data and analytical resources by all elements of the project, as appropriate.
• Include a plan for ensuring experimental rigor and control of bias (e.g., with sample size estimation and data handling).
• Describe plans for maintenance of close collaboration and effective communication among members of the team through meetings, including frequency and types of contact between participating researchers, and documenting and disseminating meeting proceedings. In addition, provide working plans for project completion following the loss of a key member of the group.
• Include a plan for completion of the research project should a key member leave the group, including plans to replace the PD/PI if needed.
• Describe how the proposed collaborative work will address questions that would be difficult to answer with data from a single site.

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

Applicant should allot funds for participation in Network activities as detailed in the Cooperative Agreement terms, with further fund allocations for data harmonization and potential collaborative, cross-network analyses.

Specific Aims:

The collaborative mechanism requires an Overview section as part of the specific aims attachment. This attachment must provide: 1) an overall rationale for applying as a collaborative study; 2) outline the role of each site and how they will contribute to achieve the FOA objectives; 3) Specific Aims of the collaborative project. This Specific Aims attachment must be identical in each of the applications that are linked together in a collaborative U01 set.

Research Strategy:

Applications from each site must contain a Research Strategy that clearly describes those aspects of the project that are common to all sites of the linked applications.

The Research Strategy must be identical across linked collaborative U01 applications, with the exception of the section under the strongly encouraged header "Elements Unique to This Site." All variations in the Research Strategy between sites, no matter how minor, should be highlighted in a subsection of the Research Strategy with the heading "Elements Unique to This Site" (estimated to be no more than 1 page of the Research Strategy Section). In this subsection, PDs/PIs should describe, for example, how the research site has a unique role in the collaboration, such as data coordination, statistical analyses, etc. Any site that contracts out some portions of this work should list this fact under "Elements Unique to This Site," and provide a full description of the nature, purpose, and oversight of this contractual arrangement.

Applicants are required to submit research projects that will accelerate gene discovery for psychiatric disorders using population cohorts of non-European ancestries. Applicants should:

• Describe unique features in the proposed population that will contribute to accelerating gene discovery for psychiatric disorders globally
• Describe the plans for assessing genome-wide contributions of disease risk using cutting-edge technologies and approaches.
• Describe the rationale, strategies, and methodologies for collecting and analyzing the genomic data that will be utilized in the proposed analyses.
• Describe innovative strategies that will be utilized for the analysis of ancestrally diverse data and how admixture in the study populations will be addressed..
• Describe how these methods will support the identification of a full spectrum of ancestrally diverse data.
• Describe how these methods will support the identification of a full spectrum of ancestry-specific genomic associations for psychiatric disorders.
• Describe how individual ancestry of study participants will be determined and what measures will be implemented to account for potential ancestry driven confounding effects in the analyses.
• Describe how the planned analyses will provide insight into ancestry-specific genetic risk architecture and shared genetic risk across global populations.
• Describe any plans for generating new genomic data (e.g., whole genome sequencing). If generating data from existing samples, describe plans to ensure the DNA samples are of sufficiently high quality to anticipate high-quality sequencing results.
• If existing genomic data will be leveraged, describe how it will be harmonized across contributing sites or studies for the analysis
• Clearly and compellingly describe the rationale, strategies, and methodologies for collecting the clinical/phenotypic data that will be utilized in the proposed analyses
• Describe the data that will be utilized, such as structured interviews (e.g., Structured Clinical Interview for DSM [SCID], Diagnostic Interview for Genetics Studies [DIGS], Family Interview for Genetic Studies [FIGS]), and/or other phenotypic data such as dimensional measures (e.g. as represented in PhenX Toolkit, NIH Toolbox, RDoC)
• Justify the choice of data.
• If existing clinical/phenotypic data will be leveraged, describe how it will be harmonized across contributing sites or studies for the analysis.

Additional Application Elements:

In addition to the information provided as part of the PHS Human Subjects form, applicants MUST also include milestones regarding plans for genomic data generation. Achievement of milestones will be evaluated by NIMH, and funding of non-competing award years will depend on milestone accomplishment.

The following modifications also apply:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. All projects will be expected to incorporate broad data and sample sharing as permitted by national and local policies and regulations.
• Plans should include sharing clinical and genotypic data and bio-samples with the NIMH Repository and Genomics Resource ( NRGR ), genotype-phenotype data with the database of Genotypes and Phenotypes (dbGaP), and/or clinical and associated genotype and phenotype data to the NIMH Data Archives (NDA), as appropriate.
• The NIH Genomic Data Sharing Policy (NOT-OD-14-124) will apply to any large scale human or non-human genomic data generated under this project, as well as the use of these data for subsequent research (https://osp.od.nih.gov/scientific-sharing/genomic-data-sharing/).
• Applicants should refer to the NIMH guide notice NOT-MH-15-012; NOT-MH-08-007; and NOT-MH-13-002 for NIMH specific data and biospecimen sharing expectations.

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.

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.

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.

3. Unique Entity Identifier and System for Award Management (SAM)

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

4. Submission Dates and Times

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. Each application of a collaborative set must be on-time. Considerations for late applications that are based on the institution or PD/PI apply only to his/her individual application.

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.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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.

7. Other Submission Requirements and Information

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, NIH. Each application of a collaborative set must be complete and compliant applications that are incomplete or non-compliant will not be reviewed.

Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide.

Section V. Application Review Information

1. Criteria

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.

Significance

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?

Investigator(s)

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?

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?

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Approach

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 study design appropriate and the population well described for the proposed study?
• Are there adequate plans for assessing genome-wide contributions of disease risk using cutting-edge technologies and approaches? Does the proposed project adequately address issues of statistical power? Is the proposed experimental design adequately addressing and correcting for in sample ancestral heterogeneity?
• If new data collection is proposed, does the project provide compelling justification and appropriate strategies, and methodologies for collecting the clinical/phenotypic data that will be utilized in the proposed analyses? Is the depth of available clinical and phenotypic data enough to support the analysis plan and overall genetic discovery?
• If existing data is to be used, how appropriate are the plans for phenotypic and genetic data harmonization for any existing data sets? Is there an ability to re-contact participants for additional phenotyping or collection of additional samples?
• Are analysis plans for admixed populations adequately described to handle the unique challenges of such populations?
• Are the plans for data harmonization of genomic and phenotypic from existing data sets well described? For analysis of existing samples, are the DNA samples of sufficiently high quality to anticipate high quality sequencing results? Are there clear plans for validation of novel rare and de novo variants that are discovered?
• How appropriate are any plans describe for any generation of new genomic data? Are the rationale and methodology for the collection of new phenotypic data appropriate?

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?

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?

Project Management Plan

Is the Project Management Plan adequate and appropriate to ensure coordination of the different elements of the project? To what extent would this plan ensure that all elements would operate in a synergistic and integrated manner? To what extent does the plan include adequate procedures to ensure reliability and quality control, comprehensive transparency of data reporting, and sharing of resources? To what extent does the application include adequate plans for maintenance of close collaboration and effective communication among members within and across application sites? To what extent are the plans for data standards and data integration adequate to the need of the project? To what extent are adequate plans presented for the completion of the project following the loss of a key member of the group?

Does the research plan justify the need for a collaborative multi-site project?

Study Timeline

Does the project propose realistic timelines and milestones? To what extent do the milestones adequately encompass all critical aspects of the project?

Protections for Human Subjects

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.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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.

Vertebrate Animals

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.

Biohazards

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

Resubmissions

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

For Renewals, the committee will consider the progress made in the last funding period.

Revisions

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

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) Genomic Data Sharing Plan (GDS).

Authentication of Key Biological and/or Chemical Resources:

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.

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.

2. Review and Selection Process

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

• 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.

• 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.

3. Anticipated Announcement and Award Dates

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

Section VI. Award Administration Information

1. Award Notices

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.

2. Administrative and National Policy Requirements

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.

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.

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.htmlhttps://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.

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 Parts 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's 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 to:

• Define objectives, approaches, and to plan and conduct the proposed research and assume responsibility and accountability to the applicant organization and to the NIMH for performance and proper conduct of all research supported in this initiative, in accordance with the Terms and Conditions of Award.
• Provide interim progress updates when requested by NIMH or at a frequency determined by NIMH.
• Provide leadership in thoughts, ideas, and actions, working with the Steering Committee for the cooperative agreement.
• Coordinate and attend at least monthly Steering Committee meetings. The PD/PIs will be responsible for preparing concise proceedings or minutes (two or three pages), which will be delivered to all members within one week of the meeting.
• Attend and participate in in-person meetings amongst the PIs awarded under this initiative and the companion FOA, PAR-19-NNN, with the frequency determined by the Steering Committee.
• Accept close interaction with, and participation of, a NIMH Project Scientist in the Steering Committee to facilitate coordination amongst the grantees and other projects with related goals.
• Communicate and publish major findings in a timely manner. Publication or oral presentation of work done under this agreement will be accompanied by an appropriate acknowledgment of NIMH support, including the assigned cooperative agreement award number.
• Share data and resources generated under this project with the scientific community, as permitted by law, in a timely manner and as directed under the applicable NIMH and NIH policies sharing policies.

Data Ownership and review

• Ownership of all analytic tools, protocols, and assays developed during the course of the research rests with the respective PD/PI(s) who generated them.
• The Awardee Institution and/or Research Project Leader's Institution will retain primary custody of, and have primary rights to, data as specified under the NIMH approved data and research resource sharing plans (described above). The Government, via the NIMH Project Scientist(s), will have access to data generated under this cooperative agreement and may periodically review the data 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 NIMH Project Scientist (or designated alternate in the event that the Project Scientist is not available) will have substantial programmatic/scientific involvement to:

• Serve as a resource with respect to other ongoing NIH activities that may be relevant to this effort to effectively leverage existing NIH resources and infrastructures and provide expert advice to the awardees on specific scientific and/or analytic issues.
• Assist in the design, development, and coordination of the different stages of the study within their role as Project Scientist and a participant on the Steering Committee.
• Review analysis plans to ensure that they are within the scope of this effort and consistent with the results of peer review.
• Serve as a voting member of the Steering Committee.
• Participate in Steering Committee meetings and conference calls.

In addition, an NIMH Program Officer has usual stewardship responsibility for monitoring the conduct and progress of the project to ensure milestones are accomplished in accordance with the timeline. The Program Officer carries primary responsibility for periodic review and approval of the study protocol in relation to stated recommendations regarding continuance of the project, receives all required reports and determines that satisfactory progress is being made, and attends the Steering Committee meetings as a non-voting participant. The Program Officer negotiates throughput, quality control, validation, and cost goals with the awardees as necessary, suggests reprogramming efforts, including options to modify projects/programs when certain objectives of this FOA are not being met, and may recommend withholding of support, suspension, or termination of a U01 award for lack of adherence to required policies and/or procedures.

Areas of Joint Responsibility include:

All awardees under this FOA and the companion FOA ( PAR-20-026 ) will form a governing Steering Committee composed of the PDs/PIs, NIMH Project Scientist(s), and the NIMH Program Officer to assist in monitoring and developing scientific content and direction of the program. The PD/PI and any MPI are required to serve as members of the Steering Committee. Additional members may be added at the discretion of the Steering Committee. The Steering Committee will select, by majority vote, a Chair from among the PDs/PIs. It is expected that decisions made or actions taken by the Steering Committee will be by consensus, or majority vote when needed. Each project (project being either a single U01 or a collaborative U01 set supported under this FOA or the companion FOA [P AR-20-026 ] will have one vote, with the NIMH Project Scientist (or alternate) having one vote. The NIMH Program Officer will not have a vote. Meetings of the Steering Committee will be held monthly by teleconference calls, with in person meetings also expected to occur during the course of the award period. Applicants should budget accordingly to include travel expenses to attend. .Outside consultants/experts may be asked to participate in Steering Committee meetings and discussions, but do not have a vote on committee decisions. Membership on the Steering Committee becomes effective upon issuance of the Notice of Grant Award.

The Steering Committee will:

• Set research priorities and milestones, decide optimal research approaches and protocol designs, periodically review progress, and contribute to the adjustment of research protocols or approaches as warranted.
• Schedule and organize an in-person meeting to be held in conjunction with all projects awarded under this FOA and the companion FOA ( PAR -20-026 ) for the purpose of dissemination of ideas and encouragement of scientific collaboration. The frequency of these meetings (annual, semi-annual, etc.) will be determined by the Steering Committee, who will be responsible for scheduling the time and place and for preparing concise proceedings or minutes (action items and one-two page summary) which will be delivered to the members of the Committee within 2 weeks of the meeting.

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.

3. Reporting

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.

Section VII. Agency Contacts

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]

Miri Gitik, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-827-3523
Email: [email protected]

Nick Gaiano, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-827-3420
Email: [email protected]

Terri Jarosik
National Institute of Mental Health (NIMH)
Telephone: 301-443-3858
Email: [email protected]

Section VIII. Other Information