Key Dates

Related Announcements

NOT-MH-08-007

NOT-MH-13-002

Issued by

National Institute of Mental Health (NIMH)

Purpose

This Request for Information (RFI) seeks public comments on the biospecimen submission, access and maintenance processes for the NIMH Repository and Genomics Resource (NRGR), in order to consider options to ensure success of the continuing mission of the NRGR.

Response to this RFI is voluntary. Respondents are free to address any or all of the topics listed in the request or any other relevant topics respondents recognize as important for NIMH to consider for NRGR biospecimen submission, access, and management. Respondents should not feel compelled to address all items. Instructions on how to respond to this RFI are provided at the bottom of this Notice.

Background

Identification of genetic and environmental contributions to the etiology of brain disorders remain a public health challenge. 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 biospecimens and data into a common analytical framework is often critical to achieve sample sizes that have adequate statistical power

In 1989, NIMH launched the Human Genetics Initiative (HGI) with the goal of creating a centralized national biorepository aimed at accelerating gene discovery through the sharing of clinical information, DNA biospecimens, and cell lines coordinated through an electronic database. A stem cell repository for induced pluripotent stem cells (iPSCs) and related resources was added in 2011. Collectively, these resources are now referred to as the NIMH Repository and Genomics Resource(NRGR) and serve as the largest biorepository in psychiatry. The NRGR provides controlled 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.

To ensure the continued growth of the NRGR, NIMH laid out expectations for biospecimen sharing from NIMH funded research in two policies (NOT-MH-08-007, NOT-MH-13-002). These policies set forth expectations and responsibilities to ensure the broad and responsible sharing of biospecimens and renewable resources through the NRGR in a timely manner. Fundamental to NIMH’s stewardship of these data is respect for and protection of research participants’ interests. To date, the NRGR has distributed almost one million biospecimens to over 450 investigators world-wide and supported over 800 publications, including many high-profile papers in psychiatric genetics.

Recent advances in psychiatric genetics have highlighted the need for large sample sizes and for greater diversity in our genetic biospecimens. NIMH funded genomics projects have grown from assessing a few thousand participants to assessing tens of thousands. Until now the NRGR has absorbed the additional costs of increasing sample size of projects through enhanced technological efficiency, but as participation in the biorepository has been enthusiastically embraced, NIMH sample sizes have outpaced gains in efficiency by more than double in the last two years. This growth in costs is no longer sustainable. Through this RFI, NIMH seeks feedback on the NRGR biospecimens submission and access processes, to inform NIMH about how to make best use of limited resources as demands for the biorepository continue to grow and evolve.

Information Requested

The NIMH invites feedback pertaining to any opportunities or challenges related to the following topics, as well as potential areas and opportunities to improve efficiency of the processes associated with these topics:

1. NRGR Biospecimen Submission: To encourage participation and utilization of the biorepository for genetic studies, biospecimens were historically shipped and processed to DNA at no charge to the submitting investigator’s grant. As sample sizes have increased, continuing this support for all projects has become untenable. Respondents are asked to consider the principles that should be applied when prioritizing NIMH resources to enable broad, well-rounded biospecimen intake that best supports future research in the near and long-term. Respondents should also include in their considerations various possible methods of cost-support for the biospecimen collection (i.e., none, partial or full coverage of cost by the biorepository). Potential considerations for prioritization include:

• The scales of biospecimen collection under a single study (e.g., <500, 500-3,000, >3,000 samples submitted).
• The origin of the biospecimen (e.g., under-represented disorder, ancestral population, rare genetic syndromes)
• The biospecimen type or source (e.g., whole blood vs. saliva for DNA; extracted DNA from postmortem specimens; non-sequencing types such as plasma, urine, sequential collections for methylation)
• The potential value of the biospecimen for future genomic studies (e.g., collecting biospecimens for projects that are not presently funded for whole genome sequencing where there is extensive phenotyping)
• The methods utilized for the collection of the biospecimen (e.g., pax gene vs EDTA, latency for plasma collection)
• Whether induced pluripotent stem cell (iPSC) lines will be derived internally by the biorepository or externally by a submitting investigator. When commenting on this question, please keep in mind that intake of externally derived iPSCs to the biorepository increases overall cost of iPSC derivation and sharing for NIMH. Possible cost saving alternatives that would allow for more iPSC resource development include requirements that applicants budget in their research project grants for derivation of iPSC lines to be done as a fee-for-service by the NIMH Repository Stem Cell Core Facility in order to maintain consistency in production and quality control, ensure timely availability and eliminate the duplicative costs of intake and processing of externally produced iPSC lines.

2. NRGR Biospecimen Access: To encourage participation and utilization of the biorepository, DNA biospecimens were historically shipped to NIMH grantees at no charge to the requesting investigator’s grant. Respondents are asked to consider the principles that should be applied when prioritizing NIMH resources to enable broad biospecimen access that best supports future research in the near and long-term. Respondents should also include in their considerations various possible methods of cost-support for biospecimen access (i.e., none, partial or full coverage of cost by the biorepository). Potential considerations for prioritization include:

• Based on the current requirement at other similar biorepositories.
• Base on the scale of biospecimen distribution requested (e.g., <50, 50-500, >500 samples requested)).

3. NRGR Management: Historically, all biospecimens have been kept indefinitely at NRGR. Fresh blood biospecimens have typically been transformed into lymphoblastoid cell lines (LCLs) as a renewable resource to ensure the long-term availability of DNA for genetic studies. Alternatively, biospecimens are often processed and stored as cryo-preserved lymphocytes (CPLs) to permit the generation of renewable cell lines (e.g., LCLs, iPSCs) at a later date. As sample sizes have increased, continuing this support for all projects has become financially untenable. Respondents are asked to consider the principles that should be applied when prioritizing NIMH resources around the production of renewables and long-term storage that best supports future research in the near and long-term. Potential considerations for prioritization include:

• The likelihood that banked LCL or CPL resources of various origins (e.g., under-represented disorder, ancestral population, rare genetic syndromes) and scales (e.g., <500, 500-3,000, >3,000 samples submitted) would be necessary for future purposes (e.g., for iPSC derivation, genetic analysis). When commenting on this question, please keep in mind that LCL/CPL generation is a cost-intensive effort that limits intake of samples from other projects.
• The current and projected utilization of a biospecimen (i.e., samples that have low utilization post-project at various time scales (e.g., 5, 10, 25 or 50 years post project)).

4. General Comments. NIMH welcomes general comments on any other topics regarding NRGR biospecimen submission, access, and management.

General Information

Responses to this RFI Notice are voluntary. Submitted information will not be considered confidential. Responses are welcome from associations and professional organizations as well as individual stakeholders. This request is for information and planning purposes and should not be construed as a solicitation or as an obligation of the Federal Government or NIMH. No awards will be made based on responses to this RFI. The information submitted will be analyzed and may be used for planning purposes. You will receive an electronic confirmation acknowledging receipt of your response, but will not receive individualized feedback on your submission. No proprietary, classified, confidential and/or sensitive information should be included in your response. The NIH and the Federal Government reserve the right to use any non-proprietary technical information in any future solicitation(s).

We look forward to your input and encourage you to share this announcement with your colleagues.

Inquiries

Please direct all inquiries to:

Responses to this Notice should be submitted by email to: [email protected] with the subject line "Attention: NIMH Biorepository RFI".