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.

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.

Biospecimen Data Reporting in the Research Literature.

A substantial fraction of biomedical research depends on the reliability of human biospecimens but variations in sample manipulation during collection, processing, and storage can differentially alter molecular integrity and influence interpretation of the resulting derived data. Details of biobanking processes are rarely adequately described in research publications, preventing reviewers, readers, and scientists seeking to replicate the findings, from appreciating and adequately considering preanalytical variations contributing to results. To address these shortcomings, a set of reporting guidelines, the Biospecimen Reporting for Improved Study Quality (BRISQ) criteria, were developed in 2011. In this study we evaluated the uptake and reporting of BRISQ criteria in 324 articles across four leading biomedical journals using human biospecimens and published before (161; in 2010) and after (163; in 2014) the delineation of the BRISQ guidelines. We found that even within journals recommending use of BRISQ, manuscript-level uptake. and reporting of the relevant biospecimen information is not widespread or uniform. In the future, an enhanced biospecimen reporting strategy to better serve the needs of researchers, reviewers, and journals may be considered to strengthen research reproducibility for the benefit of the research community at large.

Business Planning for a Campus-Wide Biobank.

Biobanks are resources that facilitate research. Many biobanks exist around the world, but most tend to focus on a specific disease or research area. BC Children's Hospital and BC Women's Hospital are located on the same campus (Oak Street Campus) in Vancouver, BC, Canada. A campus-wide biobank has been established on the site of these two hospitals to collect specimens and annotated data from children or women seeking medical care at either of the hospitals. Such an initiative requires careful planning and consideration of many factors such as buy in and support of key stakeholders, governance, financial planning, and optimizing specimen collection. We developed a business plan to account for the many aspects associated with integrating the "BC Children's Hospital BioBank." This document describes the approach our business plan took for the implementation of our biobank and the progress, including deviations from the business plan. We also provide a perspective on the current status with a focus on sustainability.

Biospecimen User Fees: Global Feedback on a Calculator Tool.

The notion of attributing user fees to researchers for biospecimens provided by biobanks has been discussed frequently in the literature. However, the considerations around how to attribute the cost for these biospecimens and data have, until recently, not been well described. Common across most biobank disciplines are similar factors that influence user fees such as capital and operating costs, internal and external demand, and market competition. A biospecimen user fee calculator tool developed by CTRNet, a tumor biobank network, was published in 2014 and is accessible online at www.biobanking.org . The next year a survey was launched that tested the applicability of this user fee tool among a global health research biobank user base, including both cancer and noncancer biobanking. Participants were first asked to estimate user fee pricing for three hypothetical user scenarios based on their biobanking experience (estimated pricing) and then to calculate fees for the same scenarios using the calculator tool (calculated pricing). Results demonstrated variation in estimated pricing that was reduced by calculated pricing. These results are similar to those found in a similar previous study restricted to a group of Canadian tumor biobanks. We conclude that the use of a biospecimen user fee calculator contributes to reduced variation of user fees and for biobank groups (e.g., biobank networks), could become an important part of a harmonization strategy.

A framework for biobank sustainability.

Each year funding agencies and academic institutions spend millions of dollars and euros on biobanking. All funding providers assume that after initial investments biobanks should be able to operate sustainably. However the topic of sustainability is challenging for the discipline of biobanking for several major reasons: the diversity in the biobanking landscape, the different purposes of biobanks, the fact that biobanks are dissimilar to other research infrastructures and the absence of universally understood or applicable value metrics for funders and other stakeholders. In this article our aim is to delineate a framework to allow more effective discussion and action around approaches for improving biobank sustainability. The term sustainability is often used to mean fiscally self-sustaining, but this restricted definition is not sufficient for biobanking. Instead we propose that biobank sustainability should be considered within a framework of three dimensions - financial, operational, and social. In each dimension, areas of focus or elements are identified that may allow different types of biobanks to distinguish and evaluate the relevance, likelihood, and impact of each element, as well as the risks to the biobank of failure to address them. Examples of practical solutions, tools and strategies to address biobank sustainability are also discussed.

Reduced expression of vascular endothelial growth factor paralleled with the increased angiostatin expression resulting from the upregulated activities of matrix metalloproteinase-2 and -9 in human type 2 diabetic arterial vasculature.

Impaired angiogenesis could contribute to the increased incidence of coronary and peripheral artery disease in diabetic patients. Angiogenesis is initiated by vascular endothelial growth factor (VEGF), a potent angiogenic cytokine, and suppressed by angiostatin, which is generated by matrix metalloproteinase (MMP)-2 and -9 through proteolytic cleavage of plasminogen. We hypothesized that MMP-2 and -9 were upregulated in the diabetic vasculature, resulting in increased angiostatin production and reduced blood vessel formation. In diabetic internal mammary artery samples (n=32) collected from patients undergoing coronary artery bypass grafting surgery, capillary density was only 30% of that in the nondiabetic vessels (n=32), whereas VEGF expression was reduced by 48%. Diabetes upregulated the expression and the gelatinolytic activity of MMP-2 and -9. Active MMP-2 and -9 were released from diabetic arteries, but not from nondiabetic vessels, during phenylephrine-induced vasoconstriction. Diabetes enhanced transcription and protein expression of tissue inhibitor of MMP (TIMP)-1 but had an opposite effect on TIMP-2. In diabetic vessels angiostatin was increased by 62% and was positively correlated with the activities of MMP-2 and -9 (r2=0.806 and 0.742, respectively). This report indicated a strong correlation between the upregulation of MMP-2 and MMP-9 and the increased angiostatin expression in the human diabetic arterial vasculature. The enhanced angiostatin production with a reduced VEGF formation may explain the pathogenesis of impaired angiogenesis in diabetes mellitus.