Neurobiobank Meeting Summary
Location: Rockville, MD
National Institute of Mental Health (NIMH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
National Institute of Neurological Disorders & Stroke (NINDS)
On May 14-15, 2012, NIMH, NICHD, and NINDS convened a meeting of brain banking experts from across the United States and with experts from the European Union’s Brain Banking network, BrainNet Europe. The goal of the meeting was to discuss issues related to the efforts by the three Institutes to take a more integrated and coordinated approach to brain banking in the U.S. This increased integration and coordination will be accomplished through federation of brain banks using a centralized data management system (see Notice of Change in Funding Mechanism for Biobanks (NOT-MH-12-020)). Meeting attendees discussed topics that had been identified through extensive research and analysis by the NIH Neurobiobank workgroup including information from outside experts—including the attendees—prior to the in-person meeting. The following major conclusions came out of the meeting and will inform the development of this new model for brain banking:
Session 1: Establishing Quality Standards and Metrics
- As a first step, it was suggested that a “test set” of samples be shared across sites to generate data that can be compared; this would increase confidence in the data, establish variance, and identify differences in methods or issues that need to be addressed. A standard set of measures, such as RNA Integrity Number (RIN), tissue pH, nucleic acid 280/260 ratio, and identification of standards for protein quality will further advance this goal.
- Attendees agreed that high quality annotation of tissues is the key to empowering researchers to identify those tissues that will be of appropriate quality for their particular research questions.
Session 2: Donor Phenotyping Standards
- A sub-group will work to establish standards for phenotyping all control subjects, with regard to neuropathology and critical data elements to be applied across brain banking sites. As there are already standards for characterization of most diseases and disorders of the central nervous system, these would continue to be recognized. The goal of characterizing control subjects is to set a standard across participating brain bank sites.
Session 3: Increasing Sample Acquisition
- Outreach is important; an increased effort at both NIH and the brain bank level will be supported. The Neurobiobank Portal will facilitate these efforts.
- Broader communication among NIH, Medical Examiners, Organ Procurement Organizations, and brain bank principal investigators (PIs) should be encouraged.
- Establish an effort to educate the public about the value of research donation in accordance with the value of organ transplant donation.
- Brain bank PIs should create a task group from among the federated sites focused on this issue.
Session 4: Increase availability of tissues and data generated from donated tissues
- All attendees agreed that data acquired from donated tissues should be returned to a central database. The data sharing plan to use human tissues should include how this will be done; if a PI fails to share data derived from human tissue samples, it could be considered against him or her regarding future requests.
- Some attendees of the group felt that the NIH should distinguish between existing collections versus prospective collections for sample sharing policies (existing collections would be exempt from “having to share” high priority tissues).
- Some attendees felt that there should be some proprietary period of time to access tissues collected at their own sites.
- A two-tiered approach for granting access was suggested. If tissue is abundant and a bank can easily fulfill an order, the PI could approve it. If a request is for a large amount of tissue, required from multiple banks, or questions arise about the intended use, a Steering Committee would evaluate and make a decision about the request.
- Brain banks should avoid micromanagement, or serving as a second “peer review.”
- There are opportunities to centralize some aspects of brain banking, such as toxicology tests, neuropathology, and/or genotyping.
- There is a need to form a phenotyping sub-workgroup to establish standard phenotyping data for control subjects (neuropathology work up and critical data elements).
- A Neurobiobank Steering Committee should be formed, involving PIs of brain banks, NIH staff, and external experts. All attendees were in favor of doing this to manage complex or large tissue requests and to provide guidance.
Neuropathology Work-up for Control Donors
As an outcome of the Neurobiobank meeting, a subcommittee was formed and co-led by Harry Haroutunian, Ph.D. and Dennis Dickson, M.D. with the goal of establishing standards for characterizing control brains across all brain banking sites, thereby optimizing the value of the collected brains to basic and translational scientists. The group met over the course of 10 weeks via teleconference and reached agreement on standards and critical data elements for control and pathological tissues. Brains suspected to have some pathology either by neuropathological findings or clinical data history would be subject to subsequent analyses as appropriate.
This decision tree matrix is intended to establish a standard neuropathological characterization for controls such that researchers using the tissue will know how these are characterized regardless of which brain bank provides them.
The following is a proposed list of standard critical data elements to be collected on all donated healthy/control brains obtained through the NIH Brain and Tissue contracts:
- DSM-based diagnosis using a formal, systematized, objective, and evidence-based assessment with:
- Detailed documentation of evidence for diagnosis assignment;
- Evidence of time since disease onset and extent (years) of hospitalization when applicable;
- Detailed documentation of prioritized (clinical judgment of assessment team) comorbidities;
- Documentation of discernible pre-agonal medical status;
- Documentation of licit and illicit drug exposure;
- Documentation of source of clinical information;
- Assignment of level of confidence for each item, (low, medium, high); and
- Pertinent demographic information.
For more information, please contact Roger Little, Ph.D. at 301-402-5844, or email firstname.lastname@example.org.