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.

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 Complexity and the Evolution of Biobanks.

Biospecimens are critical in driving health research. There is increased demand for scale and quality of biospecimens that in turn drives biobanking operational costs, influences utilization, and threatens the sustainability of individual biobanks. Biospecimen research has begun to inform the details of new biobanking standards and the steps of the biobanking process that are most important to focus on to achieve higher quality. This focus on quality is currently centered mostly on intrinsic features of biospecimens and their annotating data. This review highlights additional quality features that are important to researchers in determining the fit for purpose in their research. First, we define complex qualities as those that are mostly extrinsic to the individual biospecimen and data, and second, we provide data on the growth in demand for biospecimens with this type of quality in cancer research biobanks. Finally, we discuss why biospecimen complexity is a challenge for biobanks and utilization of existing collections, and provide examples of strategies biobanks can consider to improve their focus on this aspect of quality, as we predict that researcher demand for complex biospecimens will continue to expand in the future.

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.

Research Perspective on Utilizing and Valuing Tumor Biobanks.

Tumor biobanks have become critical components of the cancer research infrastructure. Consideration of how to place appropriate values on tumor biobanks is important for all stakeholders. At the level of individual biobanks, value is important in determining how to contribute to, utilize, and fund biobanks. At the level of the research system, value is important in determining how to evaluate, rationalize, and sustain or modify the investments in this infrastructure. This review considers approaches and indicators for evaluation of a biobank with a particular focus on utilization, as one important indicator of value, from the perspective of the researcher and funder. The patterns of utilization and the influence of different phases and approaches of research, and types of biobank are described, as well as strategies for biobanks to increase utilization and therefore their value to research.

Is Your Biobank Up to Standards? A Review of the National Canadian Tissue Repository Network Required Operational Practice Standards and the Controlled Documents of a Certified Biobank.

Ongoing quality management is an essential part of biobank operations and the creation of high quality biospecimen resources. Adhering to the standards of a national biobanking network is a way to reduce variability between individual biobank processes, resulting in cross biobank compatibility and more consistent support for health researchers. The Canadian Tissue Repository Network (CTRNet) implemented a set of required operational practices (ROPs) in 2011 and these serve as the standards and basis for the CTRNet biobank certification program. A review of these 13 ROPs covering 314 directives was conducted after 5 years to identify areas for revision and update, leading to changes to 7/314 directives (2.3%). A review of all internal controlled documents (including policies, standard operating procedures and guides, and forms for actions and processes) used by the BC Cancer Agency's Tumor Tissue Repository (BCCA-TTR) to conform to these ROPs was then conducted. Changes were made to 20/106 (19%) of BCCA-TTR documents. We conclude that a substantial fraction of internal controlled documents require updates at regular intervals to accommodate changes in best practices. Reviewing documentation is an essential aspect of keeping up to date with best practices and ensuring the quality of biospecimens and data managed by biobanks.

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.

Fundamental Considerations for Biobank Legacy Planning.

Biobanking in its various forms is an activity involving the collection of biospecimens and associated data and their storage for differing lengths of time before use. In some cases, biospecimens are immediately used, but in others, they are stored typically for the term of a specified project or in perpetuity until the materials are used up or declared to be of little scientific value. Legacy planning involves preparing for the phase that follows either biobank closure or a significant change at an operational level. In the case of a classical finite collection, this may be brought about by the completion of the initial scientific goals of a project, a loss of funding, or loss of or change in leadership. Ultimately, this may require making a decision about when and where to transfer materials or whether to destroy them. Because biobanking in its entirety is a complex endeavour, legacy planning touches on biobank operations as well as ethical, legal, financial, and governance parameters. Given the expense and time that goes into setting up and maintaining biobanks, coupled with the ethical imperative to appropriately utilize precious resources donated to research, legacy planning is an activity that every biobanking entity should think about. This article describes some of the fundamental considerations for preparing and executing a legacy plan, and we envisage that this article will facilitate dialogue to help inform best practices and policy development in the future.

A Model to Estimate Frozen Tissue Collection Targets in Biobanks to Support Cancer Research.

Human biospecimens are used in 40% of cancer research publications. Tumor biobanks are an important source for these biospecimens and support both prospective and retrospective research studies. Supporting retrospective research requires tumor tissue biobanks to accrue an adequate inventory, or stock, of cases comprising tumor biospecimens and associated treatment and outcomes data. We propose a model to establish appropriate targets for stocks of frozen tissue biospecimens in tumor biobanks, sufficient to support cancer research needs. Our model considers national levels of investment in academic cancer research relative to research use of cases described in publication output, and scales this to the local context of the BC Cancer Agency Tumour Tissue Repository (TTR) as an example. Adjustment factors are then applied to correct for the primary intended user base of the biobank, as well as variables intrinsic to all biobanking operations and case collection. On this basis we estimate a current target stock for the TTR of approximately 4500 cases. Local research demand derived from case release data can then be applied to fine-tune accrual targets and refine the biobank's relative portfolio of cases from different tumor sites. We recognize that current targets will need regular remodeling as research demands change over time and that our initial model has some limitations related to the need to extrapolate from available research and biobank utilization data, and does not incorporate biospecimen/case contributions within the context of a network. However, we believe the lack of models to estimate inventory targets for tumor biobanks and to better balance research demand with biospecimen supply, contributes to the hesitation of funders to provide support, and also the problems of sustainability faced by many biobanks. Creating tangible inventory targets will improve biobank efficiency, sustainability, and may also encourage increased and stable funding.

A practical tool for modeling biospecimen user fees.

The question of how best to attribute the unit costs of the annotated biospecimen product that is provided to a research user is a common issue for many biobanks. Some of the factors influencing user fees are capital and operating costs, internal and external demand and market competition, and moral standards that dictate that fees must have an ethical basis. It is therefore important to establish a transparent and accurate costing tool that can be utilized by biobanks and aid them in establishing biospecimen user fees. To address this issue, we built a biospecimen user fee calculator tool, accessible online at www.biobanking.org . The tool was built to allow input of: i) annual operating and capital costs; ii) costs categorized by the major core biobanking operations; iii) specimen products requested by a biobank user; and iv) services provided by the biobank beyond core operations (e.g., histology, tissue micro-array); as well as v) several user defined variables to allow the calculator to be adapted to different biobank operational designs. To establish default values for variables within the calculator, we first surveyed the members of the Canadian Tumour Repository Network (CTRNet) management committee. We then enrolled four different participants from CTRNet biobanks to test the hypothesis that the calculator tool could change approaches to user fees. 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 significant variation in estimated pricing that was reduced by calculated pricing, and that higher user fees are consistently derived when using the calculator. We conclude that adoption of this online calculator for user fee determination is an important first step towards harmonization and realistic user fees.

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.