Abstract
Each fall, biobank professionals in Michigan anticipate the Great Lakes Biorepository Research Network (GLBRN) annual scientific symposium, held to promote collaborations and research opportunities and the sharing of biobanking expertise and experiences. The University of Michigan (U-M) and the U-M Medical School Central Biorepository, promoting the theme “Biospecimen Collections and Biobanking in the Era of Precision Medicine,” hosted the 2018 symposium. Over 100 registrants originating mainly from the GLBRN host institutions attended the meeting.
The format of the meeting consisted of two keynote speakers, Jonathan Keats, PhD, and Dave Chesla, BSc, MHA, PA-ASCP, AAPA, HT, who spoke on the topics of multiple myeloma genetics and the “All of Us” initiative, respectively. This was followed by four workshops centered on the Key Elements of Biobanking, Oncologic Tissue Procurement, Informed Consent, and Quality Management. This report provides highlights and key learning messages of the symposium.
The GLBRN began with four Michigan institutions (William Beaumont Health System, Van Andel Research Institute (VARI), U-M, and Michigan State University in November 2013 during the William Beaumont's Annual Biobank Symposium. Recently St. Joseph Mercy Health, Ann Arbor, joined as the fifth institutional member (Fig. 1). The rationale for the GLBRN was to improve collaboration opportunities for researchers, focus on improved quality assurance/quality control for biobank-related science, sustainability, and to develop an active interaction among peer biobanking groups.
The GLBRN leadership team—pictured from the left are George Wilson, Scott Jewell, Dan Rohrer, Tom Carey, Tim Geddes, Victoria Blanc, Barbara Pruetz, and Tom Tomlinson. GLBRN, Great Lakes Biorepository Research Network.
The GLBRN is a voluntary engagement to build a “grass root”-based organization. The organization grew organically, without external funding, and aspired to be an interactive and efficient network. One goal was to improve research by collaborating with participating institutions to provide human samples that would promote investigator-driven research as well as an opportunity to enhance management of the biobanks. The encouragement to distribute stored biospecimens is ongoing and offers the opportunity using a MOU/UBMTA-based institutional agreement to minimize barriers for the transfer of biospecimens to researchers from member institutions. However, plans to spend more time as like-minded biobankers as a resource and educational cooperative for biorepositories on a regional effort are now the primary focus of the GLBRN.
The GLBRN agreement provides advantages, as a legal document signed by the respective institutions to forge common goals, procedures, and processes developed by the institutions' biobanks, while no longer being the sole guiding principle for the members to interact. The GLBRN activity is a simple structure of interaction and contribution that any institute or research center can join by agreeing to support the set of guiding principles. Principles include the MOU/UBMTA agreement, common elements of informed consent for the collection of biospecimens, an annual informational meeting, consortium conference calls, and use and notification of materials from the GLBRN website.
Keynote Presentation #1
Dr. Jonathan Keats, Assistant Professor and Director of Bioinformatics at TGen (Phoenix, AZ) (Fig. 2), received an enthusiastic response from the audience for his keynote address “Molecular Signatures in Multiple Myeloma: The Multiple Myeloma Research Foundation (MMRF) CoMMpass Study.”1–6 His laboratory has worked to identify genetic events driving development and progression of multiple myeloma or mediating therapeutic resistance. He introduced the MMRF CoMMpass study, discussed the biobanking lessons learned during the study, and reported on important observations leveraged to develop a personalized medical treatment approach for patients with multiple myeloma.
Jonathan Keats, PhD, Assistant Professor and Director of Bioinformatics at TGen (Phoenix, AZ), received an enthusiastic response from the audience for his keynote address “Molecular Signatures in Multiple Myeloma: The Multiple Myeloma Research Foundation (MMRF) CoMMpass Study.” Dr Keats discussed why multiple myeloma is a great model disease for precision medicine because assessing the disease cell type is aided by the fact that normal plasma cells are rare in bone marrow (<2%), tumor cells can be enriched, average 94% purity (CD138), tumor cell secrets a natural, easily monitored biomarker(s), can be defined with benign precursor diseases, monoclonal gammopathy of unknown significance (MGUS), and smoldering multiple myeloma (MM).
In brief, multiple myeloma is a plasma cell cancer manifesting as frequent infections, bone problems, reduced kidney function, and anemia. Features of the disease render it a good model for studying cancer with characteristic symptoms, distinguishing cytogenetics, and easily assayed marker proteins (M proteins, beta 2 microglobin). The CoMMpass study is an observational clinical trial with ∼8 years of observation and clinical data collected every 3 months from >1000 multiple myeloma patients. Bone marrow and peripheral blood collected was quality controlled for specific markers by flow cytometry before DNA and RNA extraction and banking. Comprehensive molecular profiling at diagnosis and at each progression was made available for decision-making by physicians for patient relapses.
In his own studies, Dr. Keats reported that the most common fusion transcripts in myeloma were IgH-WHSC1. He proposed that overexpressed MAP3K14 is altered by Ig enhancers or fusion transcripts and detected NTRK1 fusions as possible therapy targets in precision medicine trials.
Keynote Presentation #2
“All of Us—Historical and Latest Developments” was presented by Dave W. Chesla, PA-ASCP, MHA, Director, Research Operations Spectrum Health Universal Biorepository (Fig. 3). The NIH funded All of Us research program is a “participant-engaged, data-driven enterprise supporting research at the intersection of human biology, behavior, genetics, environment, data science, computation and much more to produce new knowledge with the goal of developing more effective ways to treat disease.” 7 By taking into account individual variability in biological makeup, environment, and lifestyle, precision medicine aims to deliver individualized care rather than a one-size-fits-all approach to patient care. The bold mission of All of Us is to accelerate health research and medical breakthroughs, enabling individualized prevention, treatment, and care for all of us.
Dave W. Chesla, PA-ASCP, MHA, Director, Research Operations Spectrum Health Universal Biorepository, also presented a keynote address titled “All of Us—Historical and Latest Developments.” As an example, a robust QC process is critical for biobanks with formalin-fixed paraffin-embedded (FFPE) tissues. Researchers may use curls, unstained slides for macro dissection of tissues or extract cores from a block, and if QC process is not in place, cross-contamination/floaters may confound data derived from sequencing techniques. QC, quality control.
To accomplish this mission, the program needs one million or more volunteers to become partners, which will reflect the broad diversity of the United States. The program is focused on over-recruitment of populations traditionally underrepresented in biomedical research, expanding enrollment through the various partnering organizations to states and regions historically overlooked by past studies. Volunteers, who join the program as partners, have opportunities to provide data on an ongoing basis through their personalized online participant portal.
The All of Us research program is unique not only in scale (goal of one million enrolled), but also in the value of the program to the partners. The portal also allows partners access to benchmarking data. As they complete the online surveys and questions, their replies are immediately calculated versus the hundreds of thousands of others who have previously completed the questions. In addition, the program plans to perform genomic sequencing on the blood samples provided by the partners, with return of testing information back to the partner. “Not only can you participate, but there's a bidirectional flow of information that really differentiates this program.” “As a participant, I can go online through my participant portal, see my information and also glean new information about myself,” Dave Chesla said.
The data generated from the surveys, sourced health records, and testing will inform a variety of research studies. Once assembled, the All of Us research program could provide an unprecedented picture of health and wellness in the United States.
Spectrum Health (Grand Rapids, MI) is one of many regional medical centers participating in this endeavor, as part of the multistate Trans-America Consortium of the Health Care Systems Network. Led locally by site principal investigators Sandra Cottingham and Dave Chesla, Spectrum Health began offering enrollment to its West Michigan communities in September of 2017. Nationally, the program held launch celebrations in May of 2018, with live online simulcasts from each site.
Dave Chesla offered some insight into why he felt compelled to bring this program to Spectrum Health and the residents of not only West Michigan but also the nation as a whole. “Visionaries began the Framingham Heart Study, after President Truman signed off on the National Heart Act in response to the death of President Franklin Roosevelt by hypertensive heart disease and stroke.” This study and the generations of participants continue to supply valued data 70 years later. “The study has served an outsized role in strengthening modern medicine's comprehension of cardiovascular conditions.”
However, limitations of the Framingham Study exist and have influenced the All of Us research program design. The small sample size of <15,000, the geographic limitations of the recruitment strategy, and the absence of diversity limit the applicability of the knowledge to the population of the United States today. “To do a large population study of this nature, where anyone is eligible that lives in the United States, and it is agnostic to a state of disease or wellness, is unique,” Chesla said.
Workshop #1
“Considerations of Oncologic Tissue Procurement for the Pathologist” presented by Dave Chesla, discussed biospecimen collection from the surgical pathology perspective on the impact on clinical diagnosis, and how they can guide enrollment practices, optimizing the value/effort equation for biobanking sustainability. In addition, an overview of clinical laboratory practices was presented and contrasted to optimal research collections, detailing nuances that support clinical diagnosis but limit future research utility.
Mr. Chesla spoke about a value and effort grid; understanding the key elements of pathological assessment that mitigate risk and disruption of clinical testing (gross assessment, staging cutoffs, size, and location); and developing a thorough understanding of the impact of preanalytic variables and their utility. Mr. Chesla used ischemia as an example; he identified warm-clamp or devascularization, cold duration to complete freezing or fixation, formalin fixation conditions, and tissue decalcification as parameters less important as clinical variables but having substantial impact on downstream histology and molecular read outs.
Workshop #2
“Key Elements of Biobanking with Intricacies for Clinical Trials” was presented by George Wilson, Dan Rohrer, and Scott Jewell. This workshop addressed the aspects of biobanking for attendees in research and pathology laboratories by defining what is a biobank and the many considerations that go into the collection, storage, management, and distribution of biospecimens for the end user. Table 1 provides a series of topics introduced and briefly reviewed to help inform the attendees of the breadth of the operations of a biobank. The first part of the workshop noted that funding agencies, universities, pharmaceutical, and biotech companies are more than ever recognizing the importance of biobanks and the advancement in systematic quality assurance and control as a required resource needed to improve research.
Four Major Topics Followed by Short Statements About Tasks Relevant to Their Importance in Planning the Development of a Biobank Were Presented
BAL, bronchoalveolar lavage; CSF, cerebrospinal fluid; SOP, standard operating procedure; QC, quality control.
The major topics presented were important issues when planning a biobank, cost considerations when establishing a biobank, biobanking services, SOPs, and common specimen types. In addition to these topics, biospecimen kits construction and design methods based on large clinical trial and research collections were provided.
Workshop #3
“Informed Consent” presented by Barb Pruetz, Allan Loup, and Tom Tomlinson.
This panel focused on how biobanking consent differs, both in meaning and in practice, from consent in other research. The discussion highlighted that biobanking consent involves permission for research that might, but is not certain, to happen; the information disparities that arise (about specific research uses) between researcher and biospecimen donor after consent is given; and biobanking consent as trust in institutions' governance schemes. The workshop included a mock consent process, during which a volunteer deliberated and asked questions about donating to a research biobank.
Workshop #4
“Quality Management in Biospecimen Research” presented by Dana Valley and Renee Frey.
The “Quality Management in Biospecimen Research” workshop reviewed the critical components of an effective quality management system. Several real-world case studies were evaluated to demonstrate the worst-case impact that can be caused by quality system gaps and/or failures. Process mapping, innovative solutions and technologies, as well as industry resources and guidance were discussed and provided as tools for creating or improving robust systems that drive quality, consistency, and continuous improvement within the biorepository.
Concluding Remarks
GLBRN has established itself as a Michigan-based network of biobanks with considerable expertise in all aspects of biobanking. The GLBRN members provide a versatile and informed local resource to encourage and exchange ideas in a variety of different formats and promote the best practices for the collection, banking, and use of human biospecimens in basic and clinical research. Its primary function has developed to become a resource for education, advice, and a conduit to promote and facilitate interinstitutional research based on the use of biospecimens.
The GLBRN complements the national and international activity of the International Society for Biological and Environmental Repositories (ISBER) by promoting its best practices and providing an informed biobanking forum to local investigators who may be unlikely to attend an ISBER meeting. 8
Footnotes
Acknowledgments
We express our sincere thanks to Lori Moon, Van Andel Research Institute Pathology and Biorepository Core, and Leslie McCormick, University of Michigan Medical School Central Biorepository, who managed the extensive details of project management for the annual meeting and to the vendors who displayed their new and innovative offerings.
Author Disclosure Statement
No conflicting financial interests exist.