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

A major public health challenge remains in identifying the genetic and environmental contributions to the etiology of brain disorders. While recent technological advances offer promise in understanding the genetic etiology and mechanistic basis of mental disorders, realizing this potential requires the free and open sharing of genetic material, genetic and phenotypic data, and genetic analyses among researchers. This is especially true for mental disorders and other complex diseases, for which gene effect sizes are frequently modest and the integration of samples/data into a common analytical framework is often critical to achieve sample sizes that have adequate statistical power for disease association, gene mapping and mutation detection.

The evolution in the quality and quantity of genomic and phenotypic information has presented a challenge to the broad sharing of such data resources. Information is currently scattered across a plethora of heterogeneous and autonomous information systems - each with their own interfaces and control languages - that represent genetic and phenotypic information using inconsistent data models and formats. The lack of data harmonization and federation amongst databases prevents optimal utilization of the data resources currently available. Going forward, it will be necessary to provide uniform, integrated, and semantically-consistent structured data resources to fully access the power of broad data sharing and allow investigators to address the complex biology underlying mental illness.

In 1989, NIMH launched the Human Genetics Initiative (HGI) with the goal of creating a centralized national genomic resource for the scientific community aimed at accelerating gene discovery through the sharing of clinical information, DNA samples, and cell lines coordinated through an electronic database. This effort resulted in the largest biorepository in psychiatry, providing access to high-quality biomaterials collected from nearly 200,000 phenotypically well-characterized control and patient subjects from a wide-range of mental illnesses across ancestrally diverse populations. Additionally, in 2011, a stem cell repository was established to include induced pluripotent stem cells (iPSCs) and related resources. This is now the principal biorepository for gene discovery and functional genomics in mental disorders, having distributed almost a million samples to date to over 450 investigators across the globe to support approximately 1,500 genetic research studies on mental illnesses. Over 800 publications have resulted from the use of these resources, including many high profile papers in psychiatric genetics, with several hundred replicated genetic findings reported from large scale genome-wide studies.

Given the importance of this resource and its impact in the field, NIMH plans to fund one biorepository under this funding opportunity announcement (FOA), which will provide for broad sharing of biospecimens and clinical and genetic data related to mental health research and develop, sustain, and enhance research resources to accelerate gene discovery in mental disorders.

The objective of this FOA is to develop, sustain, and enhance a centralized national biorepository which will improve and enrich psychiatric genomics research resources for broad sharing with the national and international scientific community.

It is expected that the Program Director(s)/Principal Investigator(s) (PD/PI) and the proposed collaborative team have direct experience in providing to the scientific community research resources and services for genetic studies, as well as, experience in establishing a cyberinfrastructure for a mature scientific discipline.

Specific areas of scientific expertise required by the biorepository include the following:

• Molecular biology, with a primary focus on the Epstein-Barr virus transformation of lymphocytes from fresh blood samples received from national and international sites to create contaminant-free cell lines, and the extraction of high-quality DNA from these cell lines. Additional molecular biology expertise is required in extraction of nucleic acids (DNA and RNA) directly from blood with quality control procedures to assure the integrity and competence of the products in modern genetic assays.
• Tissue and cell culture, with a primary focus on initial isolation, scale-up culture and banking of primary cells from diverse types of tissue samples (e.g. skin punches, hair follicles, olfactory epithelial biopsies).
• Developmental and stem cell biology, with expertise in reprogramming, pluripotent stem cell culture, gene editing, cryopreservation, banking, reconstitution and differentiation of iPSCs with comprehensive quality control capabilities at each step.
• Laboratory informatics management including receipt of orders and distribution of biologicals with computerized-based inventory management and storage facilities with monitored and alarmed low temperature storage and fail safe procedures in place.
• Bioinformatics, with a primary focus on the receipt and production of pedigree, clinical (including information obtained from structured psychiatric interviews), genotypic and other genetic data for the establishment of documented web-based data files for the genetic analysis of mental disorders. This work will also encompass the development and application of novel technological or computational methods for the production and analysis of comprehensive genomic data sets.
• Psychiatric clinical data curation, standardization, and harmonization, with a comprehensive knowledge of cross-disorder phenotypic dimensions.
• Computer and information sciences, with a primary focus on database management and integration to enable data mining and knowledge discovery from genomic and phenotypic data on mental disorders, by constructing a cyberinfrastructure that consists of a central data repository federated with other related data repositories, computational resources, visualization environments, and researchers linked together by software and high performance networks.

NIMH aims to support building, enhancing, and sustaining biorepository resources and data management capacity for psychiatric genomics.

Biorepository Organizational Structure:

The biorepository will receive guidance from NIMH Program staff to assist with identification and implementation of appropriate strategies and priorities. This effort is expected to involve a functionally integrated, multi-disciplinary team (at one or more institutions) that will provide a single, centralized, national resource for advancing basic and translational research in the genetics of mental disorders. The biorepository is expected to include both a Biologics Element and Data Management Element. These elements should be fully integrated with each other, with all biorepository information stored in a single-centralized data warehouse and accessible to both elements through a web-based access portal. A Project Management and Organizational Structure that provides for ongoing communication and sharing of data and resources between the major elements of the biorepository and for integration of work-flows, data, and web-based systems to create a single centralized system that will be critical for success.

Critical Features of the Biorepository:

Given the many layers of data associated with biosamples, some located across multiple data repositories, a critical feature of the biorepository will be a centralized data warehouse where all data deposited at the biorepository and related to biorepository activities are stored. Further detail provided below.

Specific functions and services to be performed by the biorepository for the scientific community MUST include, but are not limited to:

Building and sustaining a Biologics Element which delivers resource capacity for psychiatric genomics.

Specifically, the Biologics Element will be responsible for using innovative, cost-effective, scalable, efficient, and high-throughput approaches for:

1) Shipping, receiving, processing, banking, and distributing to approved users, human derived biosamples (blood, saliva, biopsied material, DNA, Plasma, derived cell lines fibroblasts, lymphoblastoid cell lines [LCLs], iPSCs, etc.) from national and international research projects supported by NIMH.

2) Maintaining facilities that comply with all regulatory requirements, applicable federal, state, and local laws, and current best practices for handling biospecimens, including storing biospecimens under optimal conditions to minimize loss, damage, or contamination and providing security, back-up systems and a plan for disaster recovery.

3) Providing kits, standard operating procedures (SOP), and technical advice for biospecimen collection to registered studies supported by NIMH.

4) Processing blood samples into distributable products, such as whole blood derived DNA, plasma, whole blood derived RNA/cDNA, and renewable LCLs. This includes capabilities for storing samples as cryopreserved lymphocytes (CPLs) and deriving high quality LCLs from these CPLs.

5) Providing options for iPSC reprogramming from source cells (e.g., fibroblasts or peripheral blood mononuclear cells) and isogenic iPSC line editing, with appropriate quality control, at competitive prices.

6) Performing quality control procedures on both internally and externally produced biospecimen derivatives (DNA, plasma, RNA/cDNA, LCLs, iPSCs) to assure their genetic integrity, purity and functionality. In the case of iPSCs, quality control elements include, but are not limited to, reprogramming efficiency, self-renewal, potency, line-to-line variability, and genomic stability over passaging and post-thaw.

7) Providing options for genomic data production such as Next Generation Sequencing (NGS) applications, microarrays, etc., at competitive prices.

8) Using a laboratory informatics system and automated pipelines to ensure efficient and accurate handling and processing of the anticipated daily volume of specimens. This system will:

• Maintain high-quality, robust, flexible, and secure information systems to allow detailed tracking of sample receipt, processing, storage and distribution; rapid retrieval of samples; and metadata associated with the sample.
• Use and maintain robotic systems to separate, label, and store biospecimens and perform automated sample processing (e.g., DNA extraction).
• Use monitored and alarmed low temperature storage and fail-safe procedures.

Building and sustaining a Data Management Element that is fully integrated with the above Biologics Elements to provide easy access to the biorepository data through a single web-based portal linked to a central database.

Specifically, the Data Management Element will be responsible for:

1) Building and maintaining a single, secure central data repository with the capability to store and semantically aggregate all data and associated metadata that are generated in relation to (1) studies depositing data/samples with the repository and (2) studies utilizing resources stored at the repository. This data includes, but is not limited to:

• For all studies: the study name, investigator(s), site(s), protocol, associated publications, demographic data, clinical data (e.g., diagnostic interviews, medical history), genetic data stored with the repository, links to genetic or other data located in other databases, data tracked by the laboratory informatics system (e.g., sample types available for a subject), information about the extent and type of sharing allowable, primary and secondary analyses.
• For active studies: the number and type of samples expected and currently deposited by the study investigator, along with the status of compliance with the data sharing plans.
• For approved end-user access requests: data generated will be linked back to the resources that were accessed (e.g., study name, investigator(s), site(s), protocol, compliance with repository agreements, associated publications, data and analyses).

2) All data related to specific subjects will be linked by a unique identifier (linking-ID) which will be used to integrate data from the central repository with related data (i.e., derived from the same subjects or part or the same study) stored on other public databases (e.g., dbGaP, NIMH Data Archives, federated iPSC registries) to provide single entry-point access to all related data in a manner compliant with repository data standards and with sufficient description to enable community use.

3) Clinical/phenotypic data (e.g., multiple versions of the Diagnostic Interview for Genetic Studies (DIGS), Structured Clinical Interview for DSM Disorders (SCID), etc.) from retrospective and prospective studies (after substantial automatic curation for new studies see below) will be manually curated, standardized and harmonized into a uniform structure (e.g., mapping of diagnostic interviews to Research Domain Criteria [RDoC] dimensions) to provide enhanced querying of data across studies/disorders/phenotypic dimensions.

4) Providing a single, user-friendly, intuitive, easily navigable/searchable, web-based portal which will:

• Provide access to summary level data (open access) and individual-level data (restricted access) pertaining to data/samples stored in the biorepository
• Assure the security, privacy, and confidentiality of repository data by providing a secure login system with different customizable levels of access
• Provide comprehensive tools for querying/visualizing all data from the centrally integrated databases
• Provide tools for tracking and monitoring data/sample submissions, the utilizations of the repository resource, and the outcomes both of studies submitting data and samples and those accessing repository resources
• Provide a web-based process to gain access to restricted access individual level data and biospecimens, including comprehensive on-line instructions and automated tracking of all aspects of the request process
• Provide a phenotypic data submission system that will facilitate data standardization and incorporates substantial auto-curation of data, including establishment and maintenance of a clinical phenotype ontology and use of data dictionaries
• Provide support, both technical and instructional (e.g., tutorials), for all user groups (e.g., na ve users, experienced bioinformaticians) of the database/web-portal

It is expected that the data warehouse and web-based portal will rise to or exceed the NIH (https://gds.nih.gov/pdf/Trusted_Partner_Checklist.pdf) and Federal (FIMSA- https://cbiit.nci.nih.gov/contractor-security-guidance) standards for establishing data quality and database security.

Applicants should plan for recovery of costs and service delivery costs for services and research resources that they will provide to the scientific community.

The award under this FOA will be governed by a Genomic Steering Committee (GSC) with voting members comprised of the PD(s)/PI(s), at least four external scientists/advisors to be named after the award, and the NIMH Project Scientist.

The GSC will serve to:

• Provide advice regarding research priorities, optimal research designs, and processing milestones;
• Coordinate the activities of the Biorepository and the distribution of data, biomaterials, and services to the wider scientific community;
• Discuss scientific progress and make recommendations regarding the enhancement of research resources and the facilitation of free and open sharing;
• Assemble a Genetics Advisory Panel (GAP) of outside experts as needed to address new scientific goals.

Applications with data collection plans that involve multiple respondent groups (e.g., clients/patients, therapists/providers, supervisors, administrators) should address provisions for human subject protections and consenting procedures for all participant groups, accordingly. The NIMH has published updated policies and guidance for investigators regarding human research protection 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.

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 in response to this FOA.

Only the current awardees of the Center for Genomic Studies on Mental Disorders (U24), funded under RFA-MH-13-050, can apply. The decision to limit competition was made in consideration of the success of the current awardees in serving the psychiatric genetics community, as well as, the costs, risks, and logistical difficulties, such as substantial delays to ongoing NIMH projects supported by the biorepository, which would be incurred should the biorepository be moved to another location.

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are 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.

A minimum effort of 4 person months is required for the contact PD/PI in a multiple PD/PI application, and 3 person months for the other multiple PDs/PIs.

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, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

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:

NIMH Referral Mailbox
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.

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

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

Facilities and Other Resources: Applicants are advised that the Facilities and Other Resources section should describe both physical resources and the intellectual and collaborative resources for executing the project.

Other Attachments: Applicants must upload a single pdf attachment, with the title "Project Management and Organizational Structure that includes the following information:

Project Management and Organizational Structure:

Provide a detailed plan by which the different elements of the project, primarily the biologics element and the data management element, would operate in a synergistic and integrated manner.

The following guidelines and framework should be followed in developing this plan:

• Applications should describe the following: how procedures will be integrated across different elements within a project; overall managerial and administrative responsibilities; and procedures to assure reliability and quality control; maintenance of close collaboration and effective communication among members of the group through group meetings.
• Applications should include plans for ensuring comprehensive transparency of data reporting/sharing
• Applications should 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.

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

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

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

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

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

Research Strategy: Propose plans that describe how the valuable existing NIMH resources (www.nimhgenetics.org) and new samples and related data from projects identified by NIMH, will be supported by the biorepository. Plans must address how the proposed procedures and processes will ensure standardized banking and distribution of verified, high-quality, uncontaminated samples, as well as, verifiable genetic data and curated and harmonized phenotypic data that will advance psychiatric genetics research.

Applicants must address each of the following key areas:

Biologics Element:

• Acquisition: Describe, in general terms, procedures for timely acquisition of biomaterials (blood, saliva, biopsied material, DNA, Plasma, derived cell lines (LCL, fibroblast, iPSC) and corresponding clinical data from NIMH investigators. Include plans for providing standard operating procedures to researchers and clinicians who are not familiar with biomaterial collection for cell source (LCL, fibroblast or iPSC) or genetic material (RNA and DNA) derivation. Describe any flexibility for accepting additional biomaterial types beyond those listed above. Describe procedures for coordinating timely shipping and receiving samples to accommodate the requirements of various scientific protocols and ensure the viability and integrity of the samples and any downstream products. Describe how you will meet the needs of projects submitting samples from foreign countries (i.e., meeting local and international shipping regulations and laws; assuring sample integrity for extended shipment; receiving when necessary cell culture ampules rather than primary samples).
• Creation of distributable biosample derivatives: Describe procedures for timely processing of received blood or tissue samples to high-quality, well-characterized distributable products for the research community, such as, whole blood derived DNA, plasma, whole blood derived RNA/cDNA, primary cell cultures (fibroblast, olfactory epithelial), stable source cell-lines (CPLs), and renewable cell-lines (LCLs). Plans should also describe how innovation in derivation methods and quality control procedures will be incorporated over the time course of this award.
• iPSC support: Applicants should describe methods for the de novo derivation of iPSCs, as well as, for the characterization of externally and internally created iPSC lines (e.g., karyotyping, pluripotency testing). Plans should also describe how innovation in derivation methods, sample handling or characterization will be incorporated over the time course of this award. Applicants may also discuss plans for providing genome editing services of iPSCs using state-of-the art approaches (e.g., CRISPR/Cas9).
• Genomic Data Production: Describe data production services that you plan to provide such as Next Generation Sequencing (NGS) applications, microarrays, etc. Plans should be timely and efficient and also describe how innovation in methodologies will be incorporated over the time course of this award.
• Maintenance and Storage: Describe the plans for maintenance and storage of the existing NIMH collection (www.nimhgenetics.org) as well as samples that will be added during the course of this award. Describe safeguards against accidental loss of the collection, such as storage of duplicates at a remote site, freezer failure back-up plan, etc.
• Laboratory Management: Describe the plans for the timely tracking of sample receipt, processing, storage and distribution and for the incorporation of this data into a central data warehouse for this biorepository.

Data Management Element:

• Data Integration: Describe plans to integrate all the biorepository related data into a single queryable data structure in a timely manner. Plans should encompass data from both studies depositing data/samples with the repository and studies utilizing resources stored at the repository. Data that should be considered for this structure include, but is not limited to: 1) For all studies - the study name, investigator(s), site(s), protocol, associated publications, demographic data, clinical data (e.g., diagnostic interviews, medical history), genetic data stored with the repository, links to genetic or other data located in other databases, data tracked by the laboratory informatics system (e.g., sample types available for a subject), information about the extent and type of sharing allowable, primary and secondary analyses; 2) For active submitting studies - the number and type of samples expected and currently deposited by study investigator, along with the status of compliance with the data sharing plans; and 3) For approved end-user access requests - data generated will be linked back to the resources that were accessed (e.g., study name, investigator(s), site(s), protocol, compliance with repository agreements, associated publications, data and analyses).
• Federation of data: Describe how you will implement a unique identifier (linking-ID) for each subject in a timely manner. Describe plans to link data from the central repository with related data (i.e., derived from the same subjects or part or the same study) stored on other public databases (e.g., dbGaP, NIMH Data Archives, federated iPSC registries) in a timely manner. Plans should describe how the proposed methods and processes will provide easy logical links to data from the same subject in multiple databases. Plans should include the logistics of the interactions with other databases.
• Access Portal: Describe plans for timely development and maintenance of a single, user friendly, web based access portal to the integrated data warehouse that will assure the security, privacy, and confidentiality of repository data. Plans should include a secure login system with different customizable levels of access.

Describe how the portal will provide:

1) A searchable catalog of available samples and data from various studies:

Describe how the proposed catalog will allow timely searching of both summary level (open access) and individual-level (restricted access) data.

2) A web-based process to gain access to restricted access data and biospecimens:

Describe how the access system will provide instruction for applicants and automated tracking and monitoring of all aspects of the request process to ensure access is managed timely and efficiently.

3) A means for submitting phenotypic and genetic data as needed:

Describe how the proposed phenotypic data submission system will facilitate data standardization and provide for auto-curation of data. Plans should include provisions for establishing and maintaining a clinical phenotype ontology and for use of data dictionaries.

4) Functionality for timely tracking and monitoring of repository use in a timely manner:

Describe how the portal will gather and display data in real-time for monitoring of data/sample submissions, the utilizations of the repository resources, and the outcomes both of studies submitting data and samples and those accessing data, including publications. Describe how this tracking will gage the effect of this resource on other scientific activities that drive the field of mental health research.

5) Comprehensive tools for receiving, querying, and visualizing all data from federated databases for those with access.

• Curation of Clinical Data: Describe plans for the timely curation and harmonization of clinical/phenotypic data from diverse standard instruments (e.g., multiple versions of the Diagnostic Interview for Genetic Studies (DIGS), Structured Clinical Interview for DSM Disorders (SCID), etc.) from retrospective and prospective studies. Plans should explain how this curation and harmonization will provide enhanced querying of data across studies/disorders/phenotypic dimensions. Plans should include substantial automatic curation, as well as, manual curation.
• Security and Integrity of Data: Describe plans to implement the data warehouse and web-based portal. Applicants should refer to the NIH (https://gds.nih.gov/pdf/Trusted_Partner_Checklist.pdf) and Federal (FIMSA- https://cbiit.nci.nih.gov/contractor-security-guidance) standards for establishing data quality and database security for guidance in preparing these plans. Data management plans should also include a description of back-up system to protect against accidental loss of valuable data.

Applicants should also address:

• Customer Service: Describe plans for customer service, which will provide timely support, both technical and instructional (e.g., tutorials), for all user groups (e.g., na ve users, experienced bioinformaticians) of the database/web-portal. Plans should include a user-friendly customer service interface, such as a help-desk, to provide support to biomedical researchers who submit samples, submit data, search for samples, have technical questions regarding the submission, or who need assistance with decisions on ordering. The customer service plan must include timelines regarding turn-around time on any query.
• Publicizing the Repository: Describe plans to publicize repository collections in a timely manner. Plans should include a description of the website that will provide the face for the biorepository. A planned website should provide information describing the current status of the data available. For example a table detailing for each disorder the number of pedigrees, number of affected sibling pairs, number of affected subjects with DNA available, numbers of subjects of varying sizes of affected subjects, etc. Other efforts may include publishing notices and articles in relevant scientific journals that describe specific repository collections or the general purpose and operation of the repository, presentations at scientific meetings to represent the repository, or other activities. Describe how these activities will increase the use of repository collections, to promote awareness of repository services to the scientific community, and/or to aid in recruitment of additional samples for the repository collection when appropriate. These activities should be directed towards scientists and towards the public being served, i.e., those with psychiatric disorders and their friends and families. Describe how the state-of-the-art laboratory standard operating procedures developed for this endeavor will be shared and publicized. Describe plans for the distribution of the Diagnostic Interview for Genetic Studies (DIGS) and the Family Interview for Genetic Studies (FIGS) developed under the HGI.
• Cost recovery: Services and research resources will be provided to the scientific community by the biorepository on a fee-for-service basis when appropriate. Outline an overall cost-recovery program that provides a plan for a charge-back of such fees when necessary.

Additionally, applicants should:

• Describe timelines for: processing from sample receipt to storage, sample request to shipping, protocol deviation to reporting to NIMH, and other activities to ensure timely responses and real-time tracking. Where possible, integrate timelines for these activities into project milestones.

Additional Application Elements:

Applicants MUST also address milestones. Specific milestones must be presented that will need to be met in order to accomplish the aims. Annual and biannual milestones should be provided in the context of a study timeline. Milestones should be well described, specific, measurable, and should include scientifically justified benchmarks. Milestones should include, but are not limited to: timely processing of sample submissions and requests; communication with NIMH and other stakeholders; integration of data; federation of data with other databases; development and implementation of the web-based access portal and its attendant informatics systems; tracking and monitoring of repository use; curation and harmonization of clinical data; and generation of DNA, RNA or cell-lines from deposited samples. The milestones should be regarded as criteria for evaluating the progress and direction of the Research Project and should not be just a restatement of the specific aims. Achievement of milestones will be evaluated by NIMH, and funding of non-competing award years will depend on milestone accomplishment.

Note that applications lacking description of required elements will be considered incomplete to this FOA and will not be reviewed.

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:

Consistent with achieving the goals of this program for this repository, applicants are required to describe a resource sharing plan that incorporates existing NIMH mechanisms and policies for data release, as already established in the NIMH Human Genetics Initiative (www.nimhgenetic.org). These mechanisms allow for the receipt by recipient of data (all demographic, diagnostic, clinical, genotypic, and family structure data) and creation of biomaterials (cell lines and DNA samples), which are distributed by recipient to qualified investigators in the scientific community. These mechanisms further specify that NIMH determines to whom and in what format such materials are distributed. It is expected that data sharing plans minimally include all phenotypic and genotypic data. All data and biomaterials managed and produced by the Biorepository are expected to be widely distributed to the national and international scientific community, consistent with achieving the goals of this program.

The Biorepository's data sharing plan should minimally include the following elements:

• comprehensive and verified databases that contain all clinical, diagnostic, and genotypic information;
• high-quality cell lines, from which DNA will be extracted and stored;
• mechanisms by which all data and any biomaterials (DNA samples and cell lines, if applicable) are widely distributed to qualified investigators in the scientific community;
• a protocol for wide dissemination of these data and applicable biomaterials;
• a timetable for distribution

The NIH Genomic Data Sharing Policy 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://gds.nih.gov/03policy2.html).

Applications which do not describe plans and resource capability to provide all the required functions and services will be considered incomplete to this FOA

Appendix:

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide. Ancillary materials, such as Standard Operational Procedures should be included in the appendix.

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

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

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

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

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

For assistance with your electronic application or for more information on the electronic submission process, visit 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 NIMH, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

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

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.

Significance

Does the proposed Center address the needs of the resource that it will serve? Is the scope of activities proposed for the Center appropriate to meet those needs? Will successful completion of the aims bring unique advantages or capabilities to the research resource? What will be the effect of these research resources on other scientific activities that drive this field?

Investigator(s)

Are the PD(s)/PI(s) and other personnel well suited to their roles in the Center? Do they have appropriate experience and training, and have they demonstrated experience and an ongoing record of accomplishments in managing critical biorepository functions, including knowledge of molecular biology, tissue and cell culture procedures, developmental and stem cell biology, psychiatric clinical data curation, laboratory informatics, bioinformatics, and computer and database structure research? Do the investigators demonstrate significant experience with coordinating collaborative basic or clinical research? If the Center is multi-PD/PI, do the investigators have complementary and integrated expertise and skills; are their leadership approach, governance, plans for conflict resolution, and organizational structure appropriate for the Center? To what extent have the PD(s)/PI(s) demonstrated experience in providing high-quality research resources and services for genetic studies on mental disorders to the scientific community? To what extent are the PD(s)/PI(s) committed to the principles of free and open sharing of research resources for genetic studies of mental disorders?

Innovation

Does the application propose novel organizational concepts or management strategies in coordinating the resource the Center will serve? Are the concepts, strategies, or instrumentation novel to one type of research program or applicable in a broad sense? Is a refinement, improvement, or new application of organizational concepts or management strategies proposed? To what extent does the proposed Center employ novel concepts, approaches, or methods for the production and sharing of research resources, the integration of biorepository data into a central warehouse, the federation of that data with other public resources, and the implementation of a single user-friendly, web-based access portal?

Approach

Are the overall strategy, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the resource the Center will serve? Will the investigators promote strategies to ensure a robust and unbiased scientific approach across the resource, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the resource is in the early stages of operation, does the proposed strategy adequately establish feasibility and manage the risks associated with the activities of the resource? Are an appropriate plan for work-flow and a well-established timeline proposed? Have the investigators presented adequate plans to ensure consideration of relevant biological variables, such as sex, for studies of vertebrate animals or human subjects?

Will the data management system proposed/developed by the Center succeed in accelerating the discovery of genes producing vulnerability to mental disorders? To what extent does the applicant utilize state-of-the-art methods to create an efficient and secure cyberinfrastructure with a single web-based portal linked to a central database in a timely manner? To what extent does the applicant propose a transparent, understandable, and timely process for data access including a user-friendly web portal? Are there reasonable and timely plans for the central database to be logically federated with other NIH databases? To what extent does the applicant propose a logical, user-friendly, and timely system for providing public access to summary level data in a way that will facilitate use of the resource by the scientific community? Are reasonable, appropriate, and timely methods described to track and monitor repository use, both submitting and accessing, and the outcomes of such use, such as data and publications?

Evaluate the molecular biological techniques described in the application for appropriateness and timeliness in assuring a high rate of success in establishing cell lines from both blood and biopsied sources. Evaluate how appropriate and timely procedures were proposed for the preparation of primary cell lines, expansion of established iPSC lines, transformation of lymphocytes cells, and extraction of nucleic acids from cell culture and blood sources. Evaluate how appropriate and timely procedures were proposed for performing quality control measures to assure cell line purity, genetic stability, and, where appropriate, reprogramming efficiency of cell lines. Evaluate how appropriate and timely procedures were proposed for the preparation of nucleic acids and quality control measures to assure purity, and competence as substrates in molecular biology assays. Evaluate how appropriate and timely procedures were proposed for transformation of primary cell to iPSCs and genome editing of iPSCs.

To what extent are there comprehensive and timely plans to integrate all functions of the data management and biological elements to operate as a singular unit? How is the system proposed for tracking incoming and distributed data and biological resources state-of the art and comprehensive and provide for real-time data? Is there an appropriate and timely plan to integrate and sustain the existing resources? Evaluate whether the plans for publicizing these resources are adequate to ensure broad use. Evaluate the adequacy of the plans for facilitating use of the resource.

Environment

Will the institutional environment in which the Center will operate contribute to the probability of success in facilitating the research resource it serves? Are the institutional support, equipment and other physical resources available to the investigators adequate for the Center proposed? Will the Center benefit from unique features of the institutional environment, infrastructure, or personnel? Are resources available within the scientific environment to support electronic information handling? To what extent does the proposed Center contain a description of the physical plant including appropriate and secure storage facilities assuring the integrity and viability of biological samples? To what extent does the proposed center's cyberinfrastructure include appropriate security measures, capacity for data integration a growth, and backup plans? Does the proposed center have a dedicated stem cell facility for high-throughput production, handling and quality control of iPSCs? To what extent does the proposed center utilize robotic automation wherever possible and have an electronic system for tracking of all biosamples? To what extent does the proposed facility have capabilities for in-house high-throughput nucleic acid extraction and cell line generation from primary source cells (CPL, LCL), with quality control? To what extent does the proposed facility have capabilities for in-house, high-throughput genome wide data generation, with state-of the-art methods?

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

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

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

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

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following 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

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

Not Applicable

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

Not Applicable

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

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).Does the sharing plan provided factor in existing resources and is it responsive to the broad sharing as desired in this FOA?

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.
• Commitment of the PD(s)/PI(s) to broad data and sample sharing and the long-term scientific mission, goals, and objectives of the NIMH.
• Adequacy of the plans to make data and biomaterials broadly available in a rapid manner to the scientific research community.
• Adequacy of plans to integrate the biomaterials and data management elements of the biorepository into a single-functional unit.
• Adequacy of plans to provide centralized data management and a user-friendly access portal.
• Adequacy of plan to sustain and integrate the existing NIMH resources (www.nimhgenetics.org) with the incoming resources.

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 http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.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 http://www.hhs.gov/ocr/civilrights/understanding/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 http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.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 purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

• Coordinating project activities scientifically and administratively at the awardee institution and among collaborators.
• Performing all activities within the scope of the research strategy specified in the application.
• Determining experimental approaches, defining objectives, designing protocols, conducting research, and overseeing the provision of services and research resources to the scientific community in accordance with the Terms and Conditions of Award.
• Providing reports as requested to NIMH staff on biorepository activities and on achievement of project milestones.
• Participating as a voting member of Genomics Steering Committee (GSC), attending GSC meetings, and assisting in developing operating guidelines, quality control procedures, and consistent policies for dealing with recurrent situations that require coordinated action.
• Coordinating at least monthly GSC meetings and one yearly in person meeting. The PD/PIs will be responsible for preparing and disseminating concise proceedings or minutes to the members and for providing travel funds for themselves and the external advisors to the yearly in-person meeting.
• Participating with other GSC members in the group process of setting research priorities and milestones, deciding optimal research approaches and protocol designs, and contributing to the adjustment of research protocols or approaches as warranted.
• Coordinating biorepository activities with the development of evolving tools and technologies in genomic and genetic science, data science, database management, and biobanking, to achieve the broad sharing goals outlined in this FOA.
• Promoting and encouraging the sharing of unique research resources for genetic studies of mental disorders by the scientific community at large.
• Developing timetables for the timely, open, and free sharing of research resources received and produced by the Biorepository to the scientific community.
• Coordinating Biorepository activities to ensure the efficient long-term storage of research resources.

Applicants responsive to this FOA agree to:

• Accept close coordination, cooperation, and participation of NIMH staff (Project Scientist(s), Program Officer(s), and/or their designee(s)) in aspects of scientific and technical management of the biorepository as described under "NIH Responsibilities" and "Joint Responsibilities" to provide for timely processing and distribution of repository resources.
• 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.
• Abide by milestones as mutually agreed by PD(s)/PI(s) and program staff.
• Accept the formation of a GSC and GAP (see collaborative responsibilities).
• Implement the common protocols guidelines and procedures approved by GSC.
• Attend meetings of the GAP as needed.
• Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

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

Project Scientist:

The role of the Project Scientist(s) will be to facilitate and not to direct activities.

Specifically, the Project Scientist(s) will:

• Provide relevant scientific expertise and serve as scientific liaison between the Biorepository and other NIH staff.
• Participate as a voting member of GSC, attend GSC meetings, and assist in developing operating guidelines, quality control procedures, and consistent policies for dealing with recurrent situations that require coordinated action.
• Participate with other GSC members in the group process of setting research priorities and milestones, deciding optimal research approaches and protocol designs, and contributing to the adjustment of research protocols or approaches as warranted.
• Coordinate Biorepository activities with the development of evolving tools and technologies in genomic and genetic science, data science, database management, and biobanking, with the scientific mission and evolving goals of the NIMH, and with other US and international efforts that focus on sharing research resources for genetic and cellular analyses of complex diseases.
• Assist in promoting and encouraging the sharing of unique research resources for genetic studies of mental disorders by the scientific community at large.
• Assist in developing timetables for the timely, open, and free sharing of research resources received and produced by the Biorepository to the scientific community.
• Assist in coordinating Biorepository activities to ensure the efficient long-term storage of research resources.

Program Officer:

The Program Officer will have responsibility for normal program stewardship. Specifically, the Program Officer will have the 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 will:

• Carry the primary responsibility for the periodic review and approval of the study protocol in relation to stated recommendations regarding continuance of the project.
• Receive all required reports and determine that satisfactory progress is being made.
• Attend the GSC meetings as a non-voting participant.
• Negotiate throughput, quality control, validation, and cost goals with the awardees as necessary and suggests reprogramming efforts, including options to modify projects/programs when certain objectives of this FOA are not being met or as scientific goals evolve.
• Evaluate and set priorities for biorepository resource generation and access of such resources by scientific community.
• Attend GAP meetings as a nonvoting member and serve as an administrative liaison.
• Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

Genomics Steering Committee (GSC)

• All collaborative activities of applicant and NIMH staff will occur through the GSC.
• The voting members of the GSC will consist of the PD(s)/PI(s), at least four external scientists/advisors to be named after the award, and the NIMH Project Scientist.
• External advisors will be selected by the PD/PI and approved by the NIMH Program Officer.
• The GSC will vote to elect a chair, who will be responsible for developing meeting agendas and chairing meetings.
• The GSC will meet, at least monthly via teleconference and at least once a year in person. Further meetings can be convened on an ad hoc basis around specific issues. The PD(s)/PI(s) will provide funds for travel themselves and for external advisors to the yearly in person meeting.
• The GSC will:
• Advise on research priorities, optimal research designs, and processing milestones;
• Coordinate the activities of the Biorepository and the distribution of data, biomaterials, and services to the wider scientific community;
• Discuss scientific progress and make recommendations regarding the enhancement of research resources and the facilitation of free and open sharing.

Genetics Advisory Panel (GAP)

• The GSC will assemble a GAP as needed, to address new scientific goals.
• The GAP members will consist of researchers or advisors selected for their broad expertise in relevant topics who are not affiliated with the Biorepository.
• These advisors will be selected by the PD(s)/PI(s) and approved by the NIMH Program Officer.
• The GAP will:
• Provide scientific advice to GSC and NIMH.
• Provide scientific and operational oversight concerning both long-term developments and distribution activities at the Biorepository.
• Provide expertise in undertaking new research or processing initiatives and incorporating emerging genomic and genetic tools and technologies into Biorepository activities.
• Assure that the needs are being met of the broader scientific community for research resources necessary for the genetic analysis of mental disorders.
• The NIMH Program Officer will attend GAP meetings as a nonvoting member and will act as a representative of NIMH and serve as the NIMH administrative liaison to the GAP if not also acting as Project Scientist.
• Other NIH staff and GSC members may attend GAP meetings, when their expertise is required for specific discussions.

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

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

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: 301-710-0267

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

David Armstrong, Ph.D.
National Institute of Mental Health
Telephone: 301-443-3534
Email: [email protected]

Terri Jarosik
National Institute of Mental Health
Telephone: 301-443-3858
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.