Key Dates

Related Announcements

NOT-MH-19-033 - Notice of Data Sharing Policy for the National Institute of Mental Health

NOT-OD-14-124 - NIH Genomic Data Sharing Policy

NOT-OD-21-013 - Final NIH Policy for Data Management and Sharing

NOT-MH-08-007 - NIMH Encourages Collection of Bio-specimens from NIMH-Supported Clinical Research Studies (RESCINDED)

NOT-MH-13-002 - Policy on Centralized Banking and Sharing of Human Subject-Derived Living Cells and Reprogrammed Derivatives for Mental Illness Research (RESCINDED)

Issued by

National Institute of Mental Health (NIMH)

Purpose

The National Institute of Mental Health (NIMH) issues this notice to replace both NOT-MH-08-007 and NOT-MH-13-002, and to alert the research community to the current NIMH prioritization and best practice guidelines for:

• Development of human induced pluripotent stem cells (iPSC)
• Sharing biospecimens (e.g., DNA, RNA, whole blood, serum, and/or iPSC)
• Requirements to apply for funding support for this sharing

NIMH strongly encourages grantees with human subjects research studies to collect and bank biospecimens and associated phenotypic information from all consenting subjects. The primary biospecimen banking resource utilized by NIMH is the NIMH Repository and Genomics Resource (NRGR), previously known as the Center for Collaborative Genomic Studies on Mental Disorders. The collection and banking of biospecimens provide a cost-effective approach to building the infrastructure for analyses of mental illnesses and will provide a significant opportunity for scientific discovery, paving the way to more effective treatments for mental disorders.

Unless NIMH stipulates otherwise during the negotiation of the terms and conditions of a grant award, this Notice applies to all grant applications and awards that involve human subject research submitted after July 11, 2021, and applies to all Funding Opportunity Announcements (FOAs) in which NIMH participates. The Notice does not apply to the following types of applications:

• Fellowship (F)
• Research Career Development (K)
• Training (T)
• Small Business (SBIR/STTR)
• Small Grants (R03)
• Education (R25)
• Awards related to AIDS applications

Biospecimen Sharing Expectations for Grant Applications

NIMH expects grantees who collect/generate human-derived biospecimens to share the biospecimens in accordance with NIH’s policy on Sharing Research Resources. NIMH strongly encourages thatsharing of biospecimens be done through the NRGR or other NIH-supported biorepositories. When determining funding priorities, consideration will be given to adherence to the field standards for biospecimen processing and quality control, as well as, the impact of duplicative costs when plans include use of biorepositories outside of the NRGR. NIMH also strongly encourages investigators planning projects with extensive deep phenotyping to collect blood samples consented for future genomic analysis and to share these biospecimens via the NRGR, even if the planned project has no current plans for genomic analysis. For biospecimen collection/generation the Resource Sharing Plan in submitted applications must include:

• Arrangements and a timeline for submitting relevant biospecimens to the NRGR or another NIH-supported biorepository, or else
• A clear rationale for why such submission will not be provided (e.g., biospecimen collection for sharing is not feasible, submission of biospecimens to outside country prohibited by law, submission to a non-NIH supported biorepository is appropriate).

Application sharing plans should describe how all collected biospecimens will be shared with the public beyond the life of the grant. An appropriate budget for the long-term biospecimen sharing described must be included in the application. NIMH expects this budget to include all costs for submission of the biospecimens to an appropriate NIH-supported biorepository during the life of the grant. Applications that propose to use biorepositories that are not NIH-supported should demonstrate funding independent of the grant, capacity for quality control, an established approval process for controlled access, an ability to appropriately link samples to data stored in NIH-supported data repositories, and the capacity and commitment (physical and financial) to support the long term storage for the duration of the expected consent of the samples. Preference will be for repositories whose samples will be readily findable by those searching NIMH databases. Plans that describe storing within individual labs and distribution by individual PIs lab following the grant period are not encouraged. Investigators who will be generating biospecimens are expected to contact the NIMH Program and the NIMH Genomic Resources Team (contact listed below) early in the planning stage and prior to budgeting for and submitting an application. Further information on costs of biospecimen submission and sharing through NRGR can be found for planning purposes at http://nimhgenetics.org. The Resource Sharing Plan will be finalized prior to the release of, and specified in, the Notice of Award. Projects that do not appropriately budget for the biospecimen collection and processing needed to complete the project aims and meet the biospecimen sharing expectations will not be prioritized for funding by NIMH.

Requirements for Biospecimens to be Banked with NRGR

For biospecimens to be deposited with NRGR, investigators will need to meet the following requirements:

• Subject consent must allow for de-identified data and resource sharing (i.e., academic and industry investigators) including use for genetic studies, wherein part or all of the genome may be sequenced, as allowed by local law and regulatory practice; Consent for broad sharing (i.e., general research use) is strongly encouraged;
• The PI and institution/facility must provide:
  • The Genome Data Sharing Certificate from the institution(s) that consented subjects, inclusive of any data use limitations;
  • Documentation of approval for biospecimen and data distribution through a NIH-controlled biorepository, inclusive of any use limitations;
  • A timeline for banking and distribution of available biospecimens, as well as, for sharing of all associated data through NRGR and/or other data repositories;

  • A description of all other databases/biorepositories where biospecimens and/or data will be submitted and shared outside of NRGR so that NRGR may prepare appropriately for linking NRGR biospecimens to these other resources in support of FAIR principles.

• Appropriate plans, budget, and timelines must be approved by NIMH program for sharing of biospecimens, as well as, necessary phenotypic data with the NRGR to ensure timely release of samples:
  • Biospecimens should be deposited to NRGR minimally 6 months before the planned public release date and prior to the end of the project period, exact requirements to be negotiated with NIMH program prior to award as part of the sharing plan
  • To carry out biobanking activities effectively (e.g., appropriate harmonization and cataloging of samples across the repository, linking of samples to existing shared data, and quality control of data), the NRGR needs access to some phenotypic data structures (e.g., demographic data, clinical instruments/interviews/surveys, diagnostic data, biospecimen meta-data, linking IDs to other repositories, biospecimen analysis values) for each sample submitted. All projects submitting biospecimens to NRGR are required to provide these data structures to NRGR at least 6 months prior to the release date unless otherwise stipulated. Projects should plan to work with NRGR to define/obtain appropriate data dictionaries for these structures early in the award period. More information on data dictionaries for NRGR can be found at http://nimhgenetics.org
  • Submission of the above required data for biospecimen sharing to NRGR does not supersede requirements to submit and share all genetic and/or phenotypic data generated under NIMH funded projects to other NIH-databases (e.g., dbGaP, NDA) per NOT-MH-19-033 and NOT-OD-14-124. As such, projects submitting biospecimens to NRGR should budget and plan for direct submission of these structures to NRGR in addition to any other direct submissions to other databases required by those notices for data sharing(e.g., NDA, AnVIL, dbGaP) unless otherwise stipulated, including any necessary reformatting of data to comply with submission requirements at each repository.
  • Depending on the level of database integration at the time of sample release between NRGR and any datarepository(ies) stipulated by the negotiated sharing plan, NRGR may or may not be able to access the above required data through sharing agreements between NRGR and the other NIH repositories. PIs should plan to complete direct submissions to NRGR using NRGR data dictionaries as described above unless otherwise directed by NRGR at the time of expected submission.

Requirement for Prior Communication and Negotiation of Grant Applications

While NIMH encourages sharing of all biospecimens, there are priorities for NIMH funding of biospecimen generation and sharing based on scientific priority areas and gaps in the biospeciment types currently available at the NRGR. PIs are strongly encouraged to contact an NIMH Scientific/Program official to discuss how their plans fit NIMH priorities prior to submitting an application.

The NRGR and support for biospecimen sharing: The operating costs of the NRGR are supported by the NIMH. In some cases, these resources may be utilized to support some or all of the biospecimen submission and processing for an individual NIMH-funded grant to lower the overall cost to NIMH for biospecimen sharing or support more biospecimen collection in high priority areas. These resources are limited and will be prioritized by NIMH program for projects that will support the development of the NRGR as a resource for our scientific community. Importantly, these resources will no longer be guaranteed available for all NIMH grantees as was the practice under the Human Genetics Initiative. Meritorious applications recommended by NIMH Program in high-priority areas may be selected after review to receive full or partial-support of sample submission activities, based on the funds available and the priorities described above, with a concurrent reduction in the individual grant budget prior to award where applicable. If your application has been selected you will be notified by an NIMH Scientific/Program official during the pre-award process.

The resources available for biospecimen sharing activities (i.e., specimen collection, DNA extraction, generation of cryo-preserved lymphocytes (CPL)), will be prioritized based on several key factors:

High priority Biospecimens from:

• Deeply phenotyped subjects (especially with dimensional phenotyping or other biomarkers), under-represented populations, and/or under-represented disorders.
• Subjects with rare genetic disorders or other factors that may be valuable for future generation of renewable cell lines (e.g. projects contributing fibroblasts, olfactory epithelial cells, LCLs, or cryo-preserved lymphocytes).

Lower priority Biospecimens from:

• Subjects with well represented DSM disorders (e.g. Schizophrenia).
• Large scale projects with light phenotyping and with funding to generate genomic data, especially whole genome sequencing.

The above factors are intended as broad guidelines. Other factors related to study design or available institutional resources may contribute to priority determinations.

Special Considerations for applications proposing generation of iPSCs: NIMH may support applications proposing the derivation of additional iPSC lines from control and/or patient populations to the extent that the polygenic architecture and heterogeneity of disease necessitates larger donor sample sizes for iPSC studies. Some studies may require new subject recruitment while others may leverage the large collection of cryopreserved source cells currently banked at NRGR. Investigators are strongly encouraged to discuss plans with Program staff early in the planning stage and prior to budgeting for and submitting an application, as follows:

• Discussions should include details about the relevant subject population, source biospecimen type, reprogramming methods, and other criteria as requested.
• All iPSC lines derived using NIMH funds should be generated using non-integrating reprogramming factors and have donor identity confirmation. Quality control measures are expected to include chromosomal integrity, pluripotency testing, clearance of reprogramming transgenes, mycoplasma and sterility testing. Detailed genetic characterization (e.g. for copy number variation, exome sequence or whole genome sequence) is strongly encouraged.
• When determining funding priorities, consideration will be given to adherence to the above standard and the impact of duplicative costs of intake, processing and quality control testing when plans include production of iPSC lines outside of the NRGR Stem Cell Core. Investigators should consider that the NRGR Stem Cell Core provides consistency in production and quality control and ensures timely availability. Investigators should budget for the entire cost of iPSC derivation and quality control measures in their grant applications.
• For generation of isogenic iPSC lines that are to be deposited in NRGR and where the disease-causing mutation is represented in NRGR iPSC lines, investigators are encouraged to perform gene editing in the available NRGR iPSC lines. Furthermore, such grant applications should budget for and propose genetic characterization (e.g. for copy number variation, exome sequence or whole genome sequencing) of the parent and edited clones. Catalog of available lines may be found at http://nimhgenetics.org.

Inquiries

Please direct all inquiries to:

General inquiries regarding this Notice may be directed to:

Jonathan Pevsner, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-728-5618
Email: [email protected]

OR

The NIMH Genomics Resources Team
Email: [email protected]

Inquiries specific to projects involving iPSCs may be directed to:

David M. Panchision, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-402-3969
Email: [email protected]