Incorporating Equity, Diversity and Inclusion in a Canadian Biobank.

Equity, diversity, and inclusion (EDI) is an established concept and is an important issue in health research. It is now recognized that measures to address EDI in research can have a positive impact on the value of health research outputs and health outcomes based on this knowledge. EDI strategies, guidelines, and education and training are now embraced by national research funders and local research organizations. However, these initiatives are very broad and not specific to the field of biobanking. We have, therefore, set out to develop and implement a formal research biobank EDI action plan. This article describes the creation of an EDI action plan that provides an intentional approach to identifying and achieving EDI actions and priorities for our research biobank. The plan is framed by the definitions of EDI and an understanding of the topics, issues, and groups within the EDI field. The plan is founded on a set of guiding principles and delineates three pillars of work that align with team, participant, and researcher domains. The plan identifies a set of 31 actions that are categorized by implementation time frames, in order to positively address EDI issues across these pillars. The completion of these actions will help us to mitigate against bias and enrich our biobanking and research services. Ultimately, our goal is to realize more diverse participation in research supported by our biobank. This would support health research to explore and better understand differences in disease biology and the efficacy of medical treatments across all people.

An Approach to Evaluate the Costs and Outputs of Academic Biobanks.

Academic biobanks commonly report sustainability challenges, which may be exacerbated by a lack of information on biobank value. To better understand the costs and supported outputs that contribute to biobank value, we developed a systematic, generalizable methodology to determine biobank inputs and publications arising from biobank-supported research. We then tested this in a small cohort (n = 12) of academic cancer biobanks in New South Wales, Australia. A proforma was developed to capture monetary and in-kind biobank costing data from biobank managers and publicly available sources. Participating biobanks were grouped and compared according to the following two classifications: open- versus restricted-access and high versus low total annual costs. Our methodology provides a feasible approach for capturing comprehensive costing data for a defined period. Characterization of biobanks using this approach showed that median total costs, as well as median staffing and in-kind costs, were comparable for open- and restricted-access biobanks, as were the quantity and journal impact metrics of supported publications. High- and low-cost biobanks supported similar median numbers of publications; however, high-cost biobanks supported publications with higher median journal impact factor and Altmetric scores. Overall, 9 of 10 biobanks had higher Field-Weighted Citation Impact scores than the global average for similar publications. This is the first tested, generalizable approach to analyze the costs and publications arising from biobank-supported research. By determining explicit cost and output data, academic biobanks, funders, and policymakers can engage in or support informed redirection of resourcing and/or benchmark setting with the aim of improving biobank support of research.

Applying Findable, Accessible, Interoperable, and Reusable Principles to Biospecimens and Biobanks.

The importance of stimulating greater sharing of data for use and reuse in health research is widely recognized. To this end, the findable, accessible, interoperable, and reusable (FAIR) principles for data have been developed and widely accepted in the research community. Research biospecimens are a resource that leads to much of this health research data but are also a form of data. Therefore, the FAIR principles should apply to biospecimens. Nevertheless, there is a widespread problem of not sharing biospecimen resources that is clearly visible within the research arena. The impacts of this are likely to include diversion of precious research funds into compiling duplicate biospecimen cohorts, detraction from research productivity as researchers compete for and create duplicate resources, and deterrence of attempts to assess research reproducibility. This article explores some of the barriers that may limit availability of FAIR biospecimens. These barriers relate to the type of biospecimen collections and the characteristics of the custodians that influence their intention and interest in sharing. Barriers also relate to the ethical, legal, and social issues concerning collections, the research context of the collections, and cost and expertise involved in repurposing collections to enable sharing. Several solutions to increase sharing are identified. Some have recently been implemented, including enhancing biospecimen locators with tools to guide researchers and facilitating transfer of research collections to centralized biobank infrastructures at the conclusion of projects. New proposed solutions include improving search capabilities within publication databases, and introduction of evidence-based justifications for all new collections into peer-reviewed grant competition processes. It is recognized that there are both scientific factors and practical reasons that can impose limits to sharing biospecimens. However, funding availability, productivity, and progress in health research all stand to benefit from improved sharing of research biospecimen collections.

Principles of reproducible metabolite profiling of enriched lymphocytes in tumors and ascites from human ovarian cancer.

Identifying metabolites and delineating their immune-regulatory contribution in the tumor microenvironment is an area of intense study. Interrogating metabolites and metabolic networks among immune cell subsets and host cells from resected tissues and fluids of human patients presents a major challenge, owing to the specialized handling of samples for downstream metabolomics. To address this, we first outline the importance of collaborating with a biobank for coordinating and streamlining workflow for point of care, sample collection, processing and cryopreservation. After specimen collection, we describe our 60-min rapid bead-based cellular enrichment method that supports metabolite analysis between T cells and tumor cells by mass spectrometry. We also describe how the metabolic data can be complemented with metabolic profiling by flow cytometry. This protocol can serve as a foundation for interrogating the metabolism of cell subsets from primary human ovarian cancer.

The different prognostic significance of polysialic acid and CD56 expression in tumor cells and lymphocytes identified in breast cancer.

Protein glycosylation, the attachment of carbohydrates onto proteins, is a fundamental process that alters the biological activity of proteins. Changes to glycosylation states are associated with many forms of cancer including breast cancer. Through immunohistological analysis of breast cancer patient tumors, we have discovered the expression of an atypical glycan-polysialic acid (polySia)-in breast cancer. Notably, we have identified polySia expression in not only tumor cells but also on tumor-infiltrating lymphocytes (TILs) and our study reveals ST8Sia4 as the predominant polysialyltransferase expressed. Evaluation of ST8Sia4 expression in tumor cells identified an association between high expression levels and poor patient outcomes whereas ST8Sia4 expression in infiltrating stromal cells was associated with good patient outcomes. Investigation into CD56, a protein known to be polysialylated, found CD56 and polySia expression on breast tumor cells and TILs. CD56 expression did not positively correlate with polySia expression except in patient tumors which expressed HER2. In these HER2 expressing tumors, CD56 expression was significantly associated with HER2 expression score. Evaluation of CD56 tumor cell expression identified a significant association between CD56 expression and poor patient outcomes. By contrast, CD56 expression on TILs was significantly associated with good clinical outcomes. Tumors with CD56+ TILs were also consistently polySia TIL positive. Interestingly, in tumors where TILs were CD56 low-to-negative, a polySia+ lymphocyte population was still identified and the presence of these lymphocytes was a poor prognostic indicator. Overall, this study provides the first detailed report of polySia and CD56 in breast cancer and demonstrates that the prognostic significance is dependent on the cell type expression within the tumor.

The Availability of Human Biospecimens to Support Biomarker Research.

Preserved biospecimens held in biobank inventories and clinical archives are important resources for biomarker research. Recent advances in technologies have led to an increase in use of clinical archives in particular, in order to study retrospective cohorts and to generate data relevant to tissue biomarkers. This raises the question of whether the current sizes of biobank inventories are appropriate to meet the demands of biomarker research. This commentary discusses this question by considering data concerning overall biobank and biospecimen numbers to estimate current biospecimen supply and use. The data suggests that biospecimen supply exceeds current demand. Therefore, it may be important for individual biobanks to reassess the targets for their inventories, consider culling unused portions of these inventories, and shift resources towards providing prospective custom biobanking services.

Finding the Value in Biobanks: Enhancing the CTRNet Locator.

Biobanks are a critical piece of Research Infrastructure (RI). However, biobanks need to accept the reality of a life cycle for RIs. Until recently, strategies to sustain biobanks have been commonly focused on ways to maintain current operational models. However, sustaining biobanks as they exist today may be increasingly challenging in the face of the disruption in health and research priorities caused by the COVID-19 pandemic. In this opinion article, we review the current and emerging future drivers of biobank value for their researchers, institutions, and funders, highlighting utilization and impact of research performed using the biobank as key measures of future value. While biobanks can only indirectly influence the specific impact of the research performed, they can transform themselves to more actively redefine utilization to their advantage. Utilization means more than the balance of samples and data in versus out. Utilization means redirecting expertise to best support end users, and importantly, closing the operating gap between biobanks and their end users who seek to find the right biospecimens and data to pursue their research. We discuss the specific role of locators (those created by public investment) in closing this gap and the need for additional tools for researchers, before and subsequent to connecting with locators. For the former, we specifically propose that more support is needed to assist researchers in the decision as to how to best obtain biospecimens and navigate the options as to whether finding existing biospecimens and data held by a biobank is the optimal solution for a given project, or whether the optimal solution is either contracting with a biobank to collect samples or creating a new biobank. We believe this type of biospecimen navigator platform will help to maximize utilization of current biobank resources, and also promote the services and expertise in biobanks to better serve researchers' needs.

Vignettes to Illustrate the Value of Tumor Biobanks in Cancer Research in Canada.

Background: Tumor biobanks are a common research infrastructure. As a collection of biospecimens and annotated data collected to support a multitude of research projects, biobanks facilitate access to materials that are the critical fuel for the generation of data in up to 40% of cancer research publications. However, quantifying how to measure biobanks' impact and their value on the field of cancer research discoveries and findings, has not been well elucidated. Methods: We have used a qualitative case study approach to illustrate the impact of tumor biobanks. We assessed the impact of three research studies published between 2010 and 2012 that required easily accessible "classic" biobanks. Each study utilized preassembled collections of tumor biospecimens with associated patient outcomes data at the outset of the research project. We compared the resulting journal impact factor, altmetric and field-weighted citation impact factor scores for each article to a set of six "benchmark" articles that represent cancer research and treatment discoveries from the same time period and two sentinel scientific discovery articles. Results: We developed a value model using a literature search and design-thinking methodologies to illustrate the contributions of these "classic" model biobanks to these research studies. Assessment of the three example articles supported by biobanks demonstrates that the output can have impact that is comparable to the impact of a set of benchmark articles describing milestones in the field of cancer research and cancer care. Conclusions: These case studies illustrate the value of the sustained investment of funds, planning, time, and effort on the part of the biobanks before the conduct of the research study to be able to ultimately support high-value research. The "value" model will enable further discussion around impact and may be useful in better delineating qualitative metrics of biobank value in the future.

Analysis of Trends in Biospecimen Complexity in Cancer Research Over Two Decades.

Background: Over time, researchers' demand for increased quality and quantity of biospecimens has risen. However, quality is multifaceted, ranging from simple to complex, and comes at a cost. Therefore, to be sustainable and ensure optimal utilization of their resources (supply), biobanks must consider the trends in biospecimen use to predict the needs for future biospecimen quality (demand). Methods: An unbiased selection process was used to identify research articles from across the spectrum of cancer research from the PubMed database. A set of 225 articles utilizing human biospecimens were randomly selected for review (75 articles from each of three time intervals; 2000, 2010, 2020). Criteria for determining the source and complexity of quality of biospecimens were developed and overall concordance between two independent observers abstracting the data was then confirmed (k = 0.87) to validate the criteria. Results: We observed increased use of dual biospecimen formats (20%-36% of articles, p = 0.03), matched samples (16%-37% of articles, p = 0.0033), and biospecimens with associated outcomes data (20%-49%, p = 0.0002). In addition, the use of two or more cohorts increased over time (p = 0.03). The mechanism through which biospecimens were obtained also changed over time with an increase in the diversity of collection pathways used (p = 0.006). Conclusions: The complexity of biospecimens being used in cancer research and the diversity of collection pathways through which these are obtained has changed significantly. This observation is important for biobanks given that the cost to support the supply of biospecimens with complex extrinsic as opposed to simple intrinsic quality characteristics is greater. For biobanks to manage sustainability, optimize utilization, and meet changing research demand, they may need to adjust their operational models to better support the supply of these types of biospecimens.

Building Research Support Capacity across Human Health Biobanks during the COVID-19 Pandemic.

Human health biobanks are forms of research infrastructure that supply biospecimens and associated data to researchers, and therefore juxtapose the activities of clinical care and biomedical research. The discipline of biobanking has existed for over 20 years and is supported by several international professional societies and dedicated academic journals. However, despite both rising research demand for human biospecimens, and the growth of biobanking as an academic discipline, many individual biobanks continue to experience sustainability challenges. This commentary will summarize how the COVID-19 pandemic is creating new challenges and opportunities for both the health biobanking sector and the supporting discipline of biobanking. While the challenges for biobanks may be numerous and acute, there are opportunities for both individual biobanks and the discipline of biobanking to embrace change such that biobanks can continue to support and drive biomedical research. We will therefore describe numerous practical steps that individual biobanks and/or the discipline of biobanking can take to survive and possibly thrive in response to the COVID-19 pandemic.

1-Methylnicotinamide is an immune regulatory metabolite in human ovarian cancer.

Immune regulatory metabolites are key features of the tumor microenvironment (TME), yet with a few exceptions, their identities remain largely unknown. Here, we profiled tumor and T cells from tumor and ascites of patients with high-grade serous carcinoma (HGSC) to uncover the metabolomes of these distinct TME compartments. Cells within the ascites and tumor had pervasive metabolite differences, with a notable enrichment in 1-methylnicotinamide (MNA) in T cells infiltrating the tumor compared with ascites. Despite the elevated levels of MNA in T cells, the expression of nicotinamide N-methyltransferase, the enzyme that catalyzes the transfer of a methyl group from S-adenosylmethionine to nicotinamide, was restricted to fibroblasts and tumor cells. Functionally, MNA induces T cells to secrete the tumor-promoting cytokine tumor necrosis factor alpha. Thus, TME-derived MNA contributes to the immune modulation of T cells and represents a potential immunotherapy target to treat human cancer.

A Permission to Contact Platform Is an Efficient and Cost-Effective Enrollment Method for a Biobank to Create Study-Specific Research Cohorts.

Background: The permission to contact (PTC) platform is a useful mechanism to increase patient engagement and enrollment into biobanks. It provides biobanks with the ability to select specific patient cohorts and to complete consent to facilitate access to biospecimens and data. In this study, we evaluated consenting costs for a biobank to compile a research cohort based on utilizing a PTC platform to obtain consent as compared with utilizing a prospective consenting approach. Methods: In this study, we utilized a PTC platform to conduct an initial selection of potential participants for two breast cancer cohorts and to provide a "referral" to the biobank to recontact these patients to provide consent to access clinical archival biospecimens and associated data. We evaluated the effort, costs, and cohorts compiled by this approach to compare this mechanism with the alternative: compiling the same type of cohorts based on a classic biobank enrollment approach. Results: After initial diagnosis and provision of a PTC up to 12 years before, recontact was possible in 84 of 90 (74%) and 77 of 107 (72%) breast cancer patients for preinvasive (ductal carcinoma in situ [DCIS]) and invasive (triple-negative subtype) cancers. Of those recontacted, consent was completed in 42 of 84 (55%) DCIS patients and 48 of 107 (45%) triple negative breast cancer (TNBC) patients. The total cost of using PTC to recontact patients to compile these two consented cohorts was CAD $26.34 and CAD $20.11 per patient consent, respectively. Conclusions: We have demonstrated the feasibility of utilizing a PTC platform to obtain informed consent from patients for a specific study through referrals provided several years after initial PTC was provided. Depending on the existing biobank operational model and the efficiency of its processes for enrollment and obtaining broad informed consent, the implementation of a PTC platform may be an efficient and cost-effective complementary method for a biobank to enroll patients to develop criteria-specific cohorts to support research.

Biobanking for Cancer Biomarker Research: Issues and Solutions.

Biomarkers are critical tools that underpin precision medicine. However there has been slow progress and frequent failure of biomarker development. The root causes are multifactorial. Here, we focus on the need for fast, efficient, and reliable access to quality biospecimens as a critical area that impacts biomarker development. We discuss the past history of biobanking and the evolution of biobanking processes relevant to the specific area of cancer biomarker development as an example, and describe some solutions that can improve this area, thus potentially accelerating biomarker research.

Improving Academic Biobank Value and Sustainability Through an Outputs Focus.

Although it is generally accepted that human tissue biobanks are important to facilitate progress in health and medical research, many academic biobanks face sustainability challenges. We propose that biobank sustainability is challenged by a lack of available data describing the outputs and benefits that are produced by biobanks, as reflected by a dearth of publications that enumerate biobank outputs. We further propose that boosting the available information on biobank outputs and using a broader range of output metrics will permit economic analyses such as cost-consequence analyses of biobank activity. Output metrics and cost-consequence analyses can allow biobanks to achieve efficiencies, and improve the quality and/or quantity of their outputs. In turn, biobank output measures provide all stakeholders with explicit and accountable data on biobank value, which could contribute to the evolution of biobank operations to best match research needs, and mitigate some threats to biobank sustainability.

Comparison and Analysis of Two Internationally Recognized Biobanking Standards.

Impactful biobanking is underpinned by quality assurance and standardization. Several general biobank standards exist that can be associated with programs to provide different levels of conformity assessment, including the Canadian Tissue Repository Network (CTRNet) Certification program and the International Organization for Standardization (ISO) 20387 and accreditation bodies. We examined the CTRNet Required Operational Practices (2017) and ISO 20387 (2018), to compare them. Although the organization of each standard is different, both describe a set of discrete requirements (elements or subclauses) that comprise the standards that are contained in sections called chapters (CTRNet) or clauses (ISO). The standards have a similar number of requirements (CTRNet: 362, ISO: 322). To compare these standards, we reclassified the requirements in the ISO standard into 13 categories based on a combination of the chapter headings used in the ISBER and NCI Best Practices that represent important areas of biobanking activity. This categorization of requirements showed that each standard has a different emphasis reflected in different densities of requirements within distinct areas of biobanking. The ISO standard emphasizes Quality Management Systems whereas the CTRNet standard has an even coverage across the full spectrum of biobanking areas, including activities that are relevant to participant enrollment. Nevertheless, ∼60% of the requirements in the CTRNet standard match with those of the ISO standard. We conclude that these two standards have much in common but recommend that individual biobanks consider each standard carefully in the context of the purpose, focus, scale, and scope of their biobank to determine the appropriate standard to be followed.

Precision medicine: Driving the evolution of biobanking quality.

The promise of precision medicine will only be realized if the healthcare system adapts to meet some key infrastructure needs. Among these needs are adequate biobanking practices, capable of producing the biological samples and data that precision medicine relies upon in both the research and clinical phases. Within the research domain, there have been significant improvements to biobanking processes over the past two decades, driven by increased understanding of the impact of pre-analytical variability and the critical role of biospecimen and data quality. In the era of precision medicine, biobanking to support clinical needs has similar quality requirements. The extensive knowledge and resources that have been developed by the research biobanking community are available for adoption by clinical biobanking. The challenge and opportunity now presented to the healthcare system is to adopt or adapt these resources, for example, external biobanking standards and verification programs.