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

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

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

Background:

The last decade has seen unprecedented progress in psychiatric genetics and large-scale team science driven efforts have begun to unravel the complex genetic architecture underlying the etiology of neuropsychiatric disorders, implicating hundreds of variants across the allelic spectrum with a broad range of effect sizes. Highly penetrant rare variants of large effect provide a unique opportunity to dissect the genetic factors influencing vulnerability and resilience to psychiatric disorders and to illuminate the underlying neurobiology of these complex disorders. For example, there are several known pathogenic variants in single genes (e.g., MECP2 and SCN2A) and pathogenic copy number variants (e.g., 3q29 Del, 16p11.2 Del/Dup, and 22q11.2 Del/Dup) that confer a substantially elevated risk for multiple clinically distinct disorders, including schizophrenia, autism spectrum disorders, anxiety, and attention deficit hyperactivity disorder. These rare genetic disorders are highly pleiotropic, with the same mutation leading to a variety of neuropsychiatric phenotypes across the life span and different mutations converging on similar phenotypic expressions. Additionally, the phenotypic presentations in these subjects often parallel those seen in idiopathic cases of mental disorders. It is posited that background common variation of small effect, as well as other rare variation and environment, shape the penetrance and expressivity of neuropsychiatric phenotypes in these rare genetic disorders.

The variable expressivity and penetrance observed for these rare genetic mutations present a unique opportunity to better understand the genetic factors underlying neuropsychiatric disorders not only in people with these rare syndromes but also in those with idiopathic psychiatric disorders more generally. Past studies in this field have been limited by small sample sizes and efforts toward meta-analyses have been hampered by a lack of field-wide standards for integration and standardization of phenotypic measures across dimensional traits, a lack of genome-wide data in general, and limited amount of data from the non-genomic factors affecting the developmental course of these phenotypes. A coordinated investigation with a detailed and comprehensive genetic and dimensional phenotypic characterization of large cohorts of individuals with rare genetic disorders is needed to amass a sufficient number of well-phenotyped patients across these rare genetic disorders to inform robust genetic analyses.

Research Objectives:

This FOA encourages collaborative research efforts to comprehensively assess the contribution of genome-wide variation to the variable expressivity and incomplete penetrance of neuropsychiatric phenotypes across rare genetic disorders using well-phenotyped clinical cohorts.

A project under this initiative MUST include both:

1) Deeper characterization of genomic-wide contributions and phenotypic dimensions across domains of psychopathology in rare genetic disorders AND

2) Study designs that consider both direct measures of psychopathology as well as broader phenotypic dimensions and seek to gain insights into variable expressivity and penetrance of these rare genetic syndromes to developing neuropsychiatric phenotypes. For example, such designs could include assessments of: a) more than one rare genetic disorder with similar phenotypic presentations (e.g., 22q11.2 del and 16p11.2 del); or b) a single genetic disorder spanning multiple diagnoses (e.g., 22q11 with autism or psychosis or ADHD). Such designs WILL include assessments of multiple phenotypic traits, combining clinical diagnostic assessments and dimensional measures.

Projects must be supported by clear evidence of the pathogenicity of the genetic variants chosen (e.g., criteria published by the American College of Medical Genetics and Genomics or/and the Association for Molecular Pathology in 2015 - PMID: 25741868, 21681106) and of the relevance of these variants to the neuropsychiatric phenotypes under investigation. Successful applicants are expected to synergize activities across disorders so that the thematic focus and rationale for including the disorders and the choice of phenotypic measures are both clear and compelling (e.g., overlapping phenotypes). Use of dimensional and quantitative phenotypes in the spirit of Research Domain Criteria (RDoC) is encouraged.

While applications submitted in response to this FOA may propose any research design that fits within the limitations described above, there are also specific areas of interest to the NIH components that are participating in this FOA. Specifically:

NIMH is particularly interested in projects seeking to explore variants which have a substantial neuropsychiatric outcome and will not consider projects exploring variants that lack primary neuropsychiatric outcomes and/or primarily result in intellectual disability.

NICHD is particularly interested in genetic and genomic variants that are associated with intellectual disability, including Down syndrome and the subset of those with Down syndrome who have co-occurring mental health conditions.

Due to the multi-disciplinary nature of the projects and the focus on collaboration, this FOA requires applicants to assemble a synergistic team of investigators (KEY PERSONNEL) with demonstrated track records (e.g., publications, education, etc.) in computational, statistical and clinical genetics, genomics, psychiatry, and other specialties as appropriate (e.g., neurology, developmental disabilities, and rare disorders).

Investigators under this initiative will form a network with a primary focus of facilitating data sharing and harmonization of clinical and genetic data across different studies in the network, as well as accelerating characterization of genotype to phenotype relationships across rare genetic disorders.

Network members that will be recruiting are strongly encouraged to generate a resource of bio-samples (e.g., DNA, blood, fibroblasts and induced pluripotent stem cells), as well as phenotypic and genetic data for broader dissemination to the scientific community through NIH designated repositories (e.g., dbGaP, ClinGen/ClinVar, NIMH Data Archives, and NIMH Repository and Genomics Resource) to the extent possible. Projects are expected to incorporate state-of-the-art integrative computational and statistical genomics methods.

Specifically, this initiative seeks collaborative and coordinated research efforts that will both:

• Conduct comprehensive analyses of genome-wide contributions to the variable penetrance and expressivity of neuropsychiatric phenotypes across rare genetic disorders. Such analyses (e.g., whole genome sequencing and mapping of breakpoints) should identify genetic factors that affect risk and resilience or modify the expression of the neuropsychiatric clinical phenotypes, taking into account the full spectrum of background genetic variation, which may include, but is not limited to:
• Common variants,
• Rare de novo and inherited variants (loss of function mutations, deletion, duplication, indels, copy number variants (CNVs) and small structural variations, etc.),

For structural variation, such as recurrent deletion/duplications, projects may also assess the effect of breakpoint variation and allelic variation of the haplotype-insufficient loci (i.e., common and rare variation in the region which is deleted on the other copy of the chromosome).

• Develop new or apply existing phenotyping methodologies to clinical cohorts that create a pipeline for standardizing assessments and linking measures across age groups to accelerate the neuropsychiatric clinical characterization of subjects with rare genetic disorders across development. Such methods include, but are not limited to:
• Assessing prospective cohorts using core phenotypic measures that may be applicable across multiple disorders (i.e., dimensional quantitative traits) and clinical diagnostic assessments,
• Harmonizing existing phenotypic data within and across disorders, including mapping to neuropsychiatric functional domains and dimensional traits that cut across multiple diagnoses (e.g., mining of large electronic medical record (EMR) systems or of data collected at clinical sites/through research programs),
• Further phenotyping of an existing cohort with diagnoses to apply a consistent battery of quantitative, dimensional assessments across sites (e.g., online assessments of RDoC functional domains)

Projects under this FOA are strongly encouraged to: 1) Incorporate broad measures of psychopathology (e.g., Social Responsiveness Scale (SRS), Personality Diagnostic Questionnaire (PDQ), and Child Behavioral Checklist (CBC)) to aid cross-network harmonization and comparisons; 2) utilize measures that may be applied across a broad range of developmental stages or to modify/tailor existing measures so that they can meaningfully translate across age groups; 3) utilize interoperable data platforms, such as common APIs, webtools, workflows, storage infrastructure, standardized data formats and meta-data standards, and standard vocabularies/ontologies to facilitate data access and integration efforts within projects and across the network, as well as with other consortia focused on rare genetic diseases, where possible. 4) utilize or adapt existing and/or develop new common vocabularies, ontologies, and Common Data Elements (CDEs) applicable across a broad array of disorders, where appropriate, (e.g., Human Phenotype Ontology [HPO], PhenX Toolkit, Neuro-QoL, NIH CDE Repository, NBSTRN CDEs, and RD-Connect CDEs); 5) leverage relevant instruments, tools, registries, and other resources developed by related NIH-sponsored programs (see list in Organization and Management section below) and collaborate with such programs, as appropriate; 6) utilize broadly consented patient registries and work with relevant patient advocacy groups (e.g., Unique and advocacy groups within other NIH programs or those aligned with the neuropsychiatric disorders of interest) for recruitment and other study goals; 7) leverage existing collaborative networks, as well as national and international collaborations, especially those that have infrastructure for consistent and high-quality sample collection and data generation and cohorts that could be re-contacted; 8) apply innovative solutions for consistent, high quality, and cost-effective phenotyping and genotyping across large cohorts of subjects (e.g., digital phenotyping, leveraging of EMR systems, leveraging mobile and web-based platforms, and partnering with consumer genomics groups); 9) make use of cost-effective recruitment strategies to ensure consistent assessments and use of standardized measures across sites.

Applicants are strongly encouraged to discuss their plans with the scientific contact designated for this FOA prior to applying.

Organization and Management of the NIMH Rare Genetic Disease Network

All awards supported under this FOA and the companion FOA (RFA-MH-19-200) will be governed by the Mental Health Rare Genetic Disease Network (MHRGDN). The role of the MHRGDN will be to facilitate harmonization efforts for measures and data across members to enhance rigor and reproducibility and generate a resource for network members and the scientific community. Network members will be expected to develop and implement best practices for data integration and harmonization across and within projects. When developing these best practices, network members are strongly encouraged to utilize methods that would enable interoperability of data sets generated by this new network with those from other NIH-funded collaborative networks studying rare diseases (see list below). While the development of new resources may be necessary, NIMH expects that network members will seek to leverage CDEs, instruments, tools, registries, and other existing resources developed by other rare disease programs where possible and, to the extent permitted, make every effort to collaborate with these existing NIH-funded efforts in areas of mutual interest, including ensuring compatibility of the data collected for rare neurodevelopmental disorders across programs. Examples of such programs include, but are not limited to:

• The Rare Diseases Clinical Research Network (RDCRN), which includes natural history and clinical studies for multiple rare diseases as well as a patient registry for rare diseases;
• The Undiagnosed Diseases Network (UDN), which identifies genomic and other causes for conditions or syndromes that can be rare or private to an individual with perplexing symptoms;
• The Newborn Screening Translational Research Network (NBSTRN), which has created a longitudinal data resource, data almanac, and CDEs for rare newborn screening conditions;
• The International Rare Diseases Research Consortium (IRDRC) and its bioinformatics tools, registries, and CDEs made available to the international rare diseases community through RD-Connect;
• The Intellectual and Developmental Disabilities Research Centers (IDDRC) Program and Network, which strives to improve developmental outcomes for children with intellectual disabilities through diagnosis, treatment, and management;
• ClinGen, which is developing curated standards and definitions of the clinical relevance of genes and genomic variants associated with many medical conditions;
• The Clinical and Translational Science Awards (CTSA) Program and Network, which works together to improve the translational research process to get more treatments to a greater number of patients more quickly and has made its bioinformatics tools, registries (ResearchMatch), databases (RedCap), and CDEs available;
• The Rare Diseases Registry (RaDaR) Program, which aims to provide easily accessible advice for constructing and maintaining good-quality rare disease patient registries to enable therapeutics development;

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-15-025). 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. Applicants collecting data and samples from minors are strongly encouraged to consider the possible need for reconsent in the future when the participants are adults and may find it necessary to plan for the use of consent forms that explicitly state that deidentified data and samples may still be used for research if re-contact is not possible (See: https://www.genome.gov/27559024/informed-consent-special-considerations-for-genome-research/). Likewise, applicants may need to take into account special considerations for participants with reduced or questionable capacity to provide informed consent (see: https://grants.nih.gov/grants/policy/questionablecapacity.htm). For linked applications, 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.

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

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

o Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Institutions)

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

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

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

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

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:

Email: [email protected]

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

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

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

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.

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:

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

Linked applications must provide an identical Project Management Plan across sites, submitted as a single 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.
• Describe the multi-disciplinary nature of the team, especially how it would comprise synergistic expertise in computational and statistical genetics, genomics, psychiatry, and psychology.
• 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 and consistent with achieving the goals of the program.
• 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.
• 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.

2. Data and Samples Plan

Linked applications must provide an identical Data and Samples Plan across sites submitted as a single pdf attachment, with the title "Data and Samples Plan" that includes the following information:

• Provide a detailed description of any available data and/or samples that will be leveraged for this project that are deidentified and thus not considered to be human subjects, including amounts, quality, type, location, procedure for acquiring, etc. This should also include a description of data and samples available at each site.

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

Personnel should document their track records in computational and statistical genetics, genomics, psychiatry, and psychology.

All instructions in the SF424 (R&R) Application Guide must be followed. Applicant should allot at least 10-15% of the proposed budget to provide funds for participation in Network activities, including, but not limited to, harmonization and integration of data with other network sites, joint analyses across network sites, as well as organization of and attendance at Network meetings (see Cooperative Agreement Terms).

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

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

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

Specific Aims:

The 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". 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 must describe how the project will characterize and more completely define the connection between genotype and phenotype for multiple rare genetic variants that convey risk for neuropsychiatric disease through a combination of comprehensive genome-wide analyses and deeper phenotypic characterization. Applicants should:

• Describe the rare genetic disorder(s) that will be included in the project and the rationale for their inclusion.
• Describe the evidence for the pathogenicity of the chosen variant(s).
• Describe the evidence for the contribution of the chosen variant(s) to the neuropsychiatric phenotypes that will be explored with the proposed phenotypic measures (e.g., effect sizes in relation to neuropsychiatric phenotypes).
• Describe how the chosen variant(s) or phenotype(s) synergize to a single thematic focus (e.g., overlapping phenotypes)
• Clearly and compellingly describe the rationale, strategies, and methodologies for collecting and harmonizing phenotypic data that will be utilized in the proposed analyses and justify the choice of the multiple phenotypic measures in the context of the chosen variant(s) (e.g., exploring both the overlap and divergence of the phenotypic spectrum).
• Identify how these measures will combine traditional diagnostic assessments with those that go beyond the DSM, such as dimensional and quantitative phenotypes in the spirit of RDoC.
• Describe any innovative solutions that will be applied for consistent, high quality, cost-effective phenotyping across large cohorts of subjects (e.g., digital phenotyping, leveraging of EMR, leveraging mobile and web-based platforms, and partnering with consumer genomics groups).
• Justify the need for any new phenotypic assessments that will be developed or piloted or new methodologies that will be used to gain phenotypic insights from existing data and describe how they will be evaluated against existing assessments and methods.
• Describe how and to what extent existing phenotypic data will be leveraged, including how it will be harmonized across contributing sites or studies and how cross-diagnostic dimensions will be extracted.
• Describe any plans to perform further phenotyping of an existing cohort with DSM diagnoses to apply a consistent battery of quantitative, dimensional assessments across sites (e.g., online assessments of RDoC functional domains).
• Describe how methods and assessments will be standardized across the project to provide consistent, well-validated phenotypes and to create a pipeline for standardizing assessments to aid cross-network data harmonization and neuropsychiatric clinical characterization of subjects with rare genetic disorders.
• Describe plans to incorporate broad measures of psychopathology (e.g., SRS, PDQ, and CBC) to aid cross-network harmonization and comparisons.
• Describe plans to utilize measures that may be applied across a broad range of developmental stages or to modify/tailor existing measures so that they can meaningfully translate across age groups.
• Describe the rationale, strategies, and methodologies for collecting and analyzing the genomic data that will be utilized in the proposed analyses.
• Describe the spectrum of genomic data that will be included in the comprehensive analyses of the genome-wide contributions to the variable penetrance and expressivity of neuropsychiatric phenotypes for the chosen rare genetic variant(s) (e.g., common variation, rare variation [loss of function mutations, small structural variations, etc.], variation in breakpoints, and allelic variation of the haplotype-insufficient loci).
• Describe any plans for generating new genomic data (e.g., whole genome sequencing and mapping of breakpoints). Where applicable (e.g., for subject populations that have previously had other types of genomic data generated for them), indicate how this genomic platform will provide new information.
• If existing genomic data will be leveraged, describe how it will be harmonized across contributing sites or studies for the analysis.
• Describe what analysis strategy will be utilized and how it will provide new insight into the genomic contributions to risk and a refined understanding of the relationship between genotype and neuropsychiatric phenotype in rare genetic disorders with neuropsychiatric phenotypes. Include a thorough assessment of statistical power.
• For both genomic and phenotypic data, describe how the project will incorporate and build upon the best practices of the appropriate fields for database management and data analyses.
• Describe any plans to utilize interoperable data platforms, such as common APIs, webtools, workflows, storage infrastructure, standardized data and meta-data formats, and standard vocabularies/ontologies.
• Describe any plans to utilize or adapt existing Common Data Elements (CDEs - see section I, Research Objectives for examples), tools, or measures applicable across a broad array of disorders, where appropriate. Include a description of the program that the resources derive from, as well as any pertinent connections the applicants have to that program.
• Describe and justify any plans to develop new CDEs, tools, measures, etc.

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

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
• Plans should include sharing clinical and genomic 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.
• Applicants are strongly encouraged to include plans to share data with databases that aggregate information on the clinical significance of genomic variation, such as ClinGen/ClinVar.
• 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-14-015; NOT-MH-09-005; NOT-MH-08-007; and NOT-MH-13-002 for NIMH specific data and bio-specimen sharing expectations.

Appendix:

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

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Section 2- Study Population Characteristics

2.5 Recruitment and Retention Plan.

Document access to a substantial subject population with the rare variants that are the focus of the application. Describe resources for outreach, recruitment, and retention of these subjects.

Describe any use of existing collaborative networks, national and/or international, with infrastructure for consistent and high-quality sample collection and data generation and re-contactable cohorts.

Section 3 - Protection and Monitoring Plans

3.1 Protection of Human Subjects

The Protection of Human Subjects attachment must be site specific, addressing the relevant circumstances, conditions, and situations of the application and applicant site. It should not be the same for all the applications within the linked applications

Provide a detailed description of any available data and/or samples that will be leveraged for this project that are considered human subject research, including amounts, quality, type, location, procedure for acquiring, etc. This should also include a description of data and samples available at each site.

If planning any prospective recruitment, re-phenotyping, or re-sampling, justify the need (e.g., missing data, inclusion of first-degree relatives, previously collected DNA or phenotypic data that is of insufficient quality or quantity and/or rare genetic disorders for which existing samples and data are limited) and provide reasonable assurance that the patients and human specimens needed for research are readily available (e.g., re-contactable cohort).

Delayed Onset Study

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

Justification Attachment

The Human Subjects information must be site specific, addressing the relevant circumstances, conditions, and situations of the application and applicant site. It should not be the same for all the applications within the linked applications.

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.

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

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

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

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

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

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

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

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

Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? 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?

How well will this project characterize and more completely define the connection between genotype and phenotype for rare genetic variants that convey risk for neuropsychiatric disease?

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?

How well does the team assembled comprise a multi-disciplinary team of experts with demonstrated track records in computational, statistical and clinical genetics, genomics, psychiatry, and other specialties as appropriate (e.g., neurology, developmental disabilities, and rare disorders)?

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?

How well will the genomic analyses allow new insight into the genotype-phenotype relationships in rare genetic disorders? Are the plans to develop new measures, CDEs, or tools well justified? Are the plans for new recruitment, new genomic data generation, or new phenotypic data generation well justified? If applicable, how does the project apply innovative solutions for consistent, high quality, cost-effective phenotyping and genotyping across large cohorts of subjects?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the 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?

How is adequate justification provided for the choice of variant(s) in relation to their pathogenicity and relevance to neuropsychiatric phenotypes? How do(es) the chosen variant(s) or phenotype(s) synergize to a single thematic focus? How does the project integrate both comprehensive genome-wide analyses and deeper phenotypic characterization? Are the phenotyping methodologies well described and justified? How will the phenotyping methodologies contribute to building consistent, well-validated phenotypic data within the project, as well as allow for harmonization of data across projects and across age groups (e.g., use of broad measures of psychopathology and measures that meaningfully translate across age groups)? Are the genomic analyses well powered? How has the project included plans to incorporate the best practices of the field for their database management and data analyses (e.g., use of existing CDEs, APIs, tool, resources, and collaborative networks)? How does the project make use of existing infrastructures?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

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

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

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 consistent with the goals of the program? 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 using this FOA?

Data and Samples Plan

Are all proposed uses of existing data and samples adequately described? For prospective data collection, how have they demonstrated access to the patient populations necessary to conduct this research?

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

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

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

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

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

Not Applicable

Not Applicable

Not Applicable

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

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

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

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

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

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

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by 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. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

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

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

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

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

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

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

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

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

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

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH'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.

All awards supported under this FOA and the companion FOA (RFA-MH-19-200) will be governed by the Mental Health Rare Genetic Disease Network (MHRGDN) Steering Committee, composed of the PDs/PIs of each project, NIMH Project Scientist(s), and the NIMH Program Officer to assist in monitoring and developing scientific content and direction of the program.

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 leadership in thoughts, ideas, and actions; working with the organization, structure, and advisors of the MHRGDN Steering Committee.
• Serve on the MHRGDN Steering Committee. The PD/PI and any MPI are required to serve as members of the Steering Committee. Key personnel from projects may also serve in addition to PD/PIs.
• Respect the governance of the MHRGDN Steering Committee and all MHRGDN policies agreed upon by the Steering Committee and approved by NIH Program Staff.
• Coordinate and attend at least monthly MHRGDN Steering Committee meetings. The PD/PIs will be responsible for preparing concise proceedings or minutes (two or three pages), which will be delivered to the members of the MHRGDN within one week of the meeting.
• Accept close interaction with, and participation of, NIH staff in aspects of management of 'within project' activities and the coordination of MHRGDN activities; cooperating and assisting in implementing the recommendations of the MHRGDN Steering Committee to facilitate coordination amongst all of the U01 grantees under this FOA and its companion RFA-MH-19-200.
• Communicate and publish major findings in a timely manner. Publication or oral presentation of work done under this agreement will be accompanied by appropriate acknowledgment of NIMH support, including the assigned cooperative agreement award number.
• 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:

• Coordinate and facilitate the interactions among the research teams supported under this FOA.
• 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 a 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(s) of the Steering Committee.
• Participate in Steering Committee meetings and conference calls.
• Serve on Steering Committee sub-committees or MHRGDN working groups and assist the Steering Committee in developing operating guidelines and consistent policies for dealing with situations that require coordinated action.

In addition, an NIMH Program Officer has usual stewardship responsibility for monitoring the conduct and progress of the project. 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 will be governed by the Steering Committee composed of the PDs/PIs of each grant, 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. Key personnel from projects may also serve in addition to PD/PIs. Each project, project being either a single U01 supported under RFA-MH-19-200 or a collaborative U01 set supported under RFA-MH-19-201, will have one vote in Steering Committee decisions. The Steering Committee will select, by majority vote, a Chair from among the PDs/PIs for a two-year term.

The Steering Committee will:

• Ensure synergistic functioning and coordination across grants supported under this FOA.
• Assist in monitoring and developing scientific content and direction of the projects.
• Identify synergies across projects.
• Coordinate across projects for data standardization and harmonization.
• Identify scientific and policy issues that need to be, or can benefit by, being addressed at the MHRGDN level and develop recommendations to Program Officials and Project Scientists for addressing such issues.
• Coordinate MHRGDN publications.
• Establish, as necessary, subcommittees to ensure progress of the individual Projects and the MHRGDN.
• Share data and resources among the members and with the broader scientific community in a timely manner, as per the data sharing plan and the Steering Committee recommendations, in accordance with the NIH and NIMH data sharing guidelines (NOT-MH-15-012; NOT-MH-14-015; NOT-MH-09-005) and GDS policy.
• Guide and evaluate the progress and direction of the research conducted by the awardees.
• Coordinate and attend monthly meetings of the Steering Committee to review progress and identify emerging opportunities for strategic partnerships and decide optimal research approaches and protocol designs as warranted.
• Schedule and organize at least one annual in-person meeting at which MHRGDN investigators will present their scientific progress and participate in group discussions.
• 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 set of collaborative U01s supported under this FOA or a single U01 supported under RFA-MH-19-200, will have one vote in Steering Committee decisions, with the NIMH Project Scientist (or alternate) having one vote. The NIMH Program Officer will not have a vote. Outside consultants/experts may be asked to participate in Steering Committee meetings and discussions but not have a vote on committee decisions. Membership on the Steering Committee becomes effective upon issuance of the Notice of Grant Award.

Dispute Resolution:

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

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

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

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

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

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Geetha Senthil, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-402-0754
Email: [email protected]

Melissa Parisi, M.D., Ph.D.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-496-1383
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]

Bryan Clark
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6975
Email: [email protected]

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

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