Biobanking and research quality: think locally, act globally.

Although biobanks can support research across geographic and governance boundaries, biomedical researchers consistently describe preferences for either collaborating with local biobanks or establishing their own biobanks. This article summarizes the potential research impacts of local biobank use and suggests how descriptions of biospecimen provenance can be improved in research publications.

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.

Opinions of Young Adults on Re-Consenting for Biobanking.

OBJECTIVE: To evaluate young adult cancer survivor opinions on whether their biobanked tissue and associated de-identified clinical data obtained during their childhood should require re-consent at the age of majority, when parental consent was originally provided. STUDY DESIGN: Thirty young adults (18-34 years old), who were former pediatric oncology patients of The Children's Hospital at Westmead with stored research biospecimens, were recruited. They completed a semistructured interview, which included questions on biobanking re-consent, awareness of biobanked tissue, satisfaction about banked tissue, and independence within the family. Analyses included descriptive and inferential statistics. RESULTS: Sixty percent of participants thought that permission for biobanking should be sought again at adulthood, and the remaining 40% did not think that re-consent was necessary. Seventy percent of participants were unaware of their previously banked tissue, which was dependent upon age at diagnosis. When asked whether they granted permission for their tissue to remain in the biobank, all participants agreed. CONCLUSIONS: Although results on whether young adults prefer to re-consent or not for previously biobanked tissue and corresponding clinical data are equivocal, survivors appear to be highly favorable about ongoing biobanking of their childhood specimens for future unspecified research.

Do clinical parameters predict first planned extubation outcome in the pediatric intensive care unit?

CONTEXT: There is absence of evidence-based guidelines to determine extubation readiness in the pediatric intensive care unit (PICU). OBJECTIVE: Evaluate our practice of determining extubation readiness based on physician judgment of preextubation ventilator settings, blood gas analysis, and other factors potentially affecting extubation outcome. DESIGN: Prospective cohort study from August 2010 to April 2012. SETTING: Academic, multidisciplinary PICU. PATIENTS: A total of 319 PICU patients undergoing first planned extubation attempt. INTERVENTIONS: None. MEASUREMENTS: Determine the extubation success rate and evaluate factors potentially affecting extubation outcome. The PICU length of stay (LOS) and cost were also recorded. Subgroup analysis was performed based on days of mechanical ventilation (MV). RESULTS: A total of 319 consecutive patients underwent first planned extubation attempt with a 91% success rate. Factors associated with extubation failure were the length of MV (P < .0001, odds ratio [OR] 2.20); age (P = .02, OR 0.54); preextubation steroids (P = .04, OR 2.40); and postextubation stridor (P < .01, OR 3.40). Ventilator settings and blood gas results had no association with extubation outcome with 1 exception, ventilator rates ≤ 8 were associated with extubation failure in patients with ≤1 day of MV. Extubation failure was associated with prolonged PICU LOS and excess cost, with failures staying 14 days longer (P < .0001) and costing 3.2 time more (P < .0001) than successes. CONCLUSIONS: Physician judgment to determine extubation readiness led to a first planned extubation success rate of 91%. Age and the length of MV were primary risk factors for failed extubation. In patients with ≤1 day of MV, our findings suggest that confidence in extubation readiness following weaning to low ventilator rates may not be justified. Furthermore, reliance on preextubation ventilator settings and blood gas results to determine extubation readiness may lead to unnecessary prolongation of MV, thereby increasing the PICU LOS and excess cost. These findings are hypothesis generating and require further study for confirmation.

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.

A Survey of Community Perceptions on Brain Donation for Research.

Postmortem brain donation for medical research is a little-known form of organ donation. While most brain research is carried out using animal models, many neurological diseases are uniquely human. Greater availability of human postmortem brain tissue from diseased individuals and controls would therefore improve the development of treatments for neurological and neuropsychiatric diseases. Globally, organ donation for medical research is dwarfed by organ donation for transplantation. In 2021, 36% of Australians were registered organ donors for transplantation, with public "in-principle" support even higher, at 76%. In contrast, there are little data on Australian or international brain donation rates for research. A 30-item online survey was conducted to ascertain knowledge of, and attitudes toward, brain donation in Australia. Of the respondents, 12/237 (5%) were current brain donors and excluded from further analysis. Of the remaining 225, 75% were registered organ donors for transplant. The vast majority (n = 189/225, 84%) of respondents supported or strongly supported the principle of brain donation. However, of those registered for transplantation or whole-body donors, 93/170 (55%) were not aware that brain donation was possible, while 50%, alternatively or also, thought that registering as an organ donor for transplantation rendered them a brain donor by default. Only 9/225 (4%) respondents indicated that they would definitely not donate their brain in the future, while 27 remained unsure. There is prominent public support for brain donation in Australia, with 84% of respondents willing to donate their brain. Yet, the extent of public misconceptions on brain donation for research suggests the need for further education on all types of organ donation, so individuals may make informed decisions.

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.

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.

What Do Biomedical Researchers Want from Biobanks? Results of an Online Survey.

Aims: The purpose of biobanking is to provide biospecimens and associated data to researchers, yet the perspectives of biobank research users have been under-investigated. This study aimed to ascertain biobank research users' needs and opinions about biobanking services. Methods: An online survey was developed, which requested information about researcher demographics, localities of biobanks accessed, methods of sourcing biospecimens, and opinions on topics including but not limited to, application processes, data availability, access fees, and return of research results. There were 27 multiple choice/check box questions, 4 questions with a 10-point Likert scale, and 8 questions with provision for further comment. A web link for the survey was distributed to researchers in late 2019/early 2020 in four Australian states: New South Wales, Victoria, Western Australia, and South Australia. Results: Respondents were generally satisfied with biobank application processes and the fit for purpose of received biospecimens/data. Nonetheless, most researchers (n = 61/99, 62%) reported creating their own collections owing to gaps in sample availability and a perceived increase in efficiency. Most accessed biobanks (n = 58/74, 78%) were in close proximity (local or intrastate) to the researcher. Most researchers had limited the scope of their research owing to difficulty of obtaining biospecimens (n = 55/86, 64%) and/or data (n = 52/85, 60%), with the top three responses for additional types of data required being "more long term follow up data," "more clinical data," and "more linked government data." The top influence to use a particular biobank was cost, and the most frequently suggested improvement was reduced direct "cost of obtaining biospecimens." Conclusion: Biobanks that do not meet the needs of their end-users are unlikely to be optimally utilized or sustainable. This survey provides valuable insights to guide biobanks and other stakeholders, such as developing marketing and client engagement plans to encourage local research users and discouraging the creation of unnecessary new collections.

Utilization of anti-Parkinson drugs in Australia: 1995-2009.

PURPOSE: To examine trends in the prescribing of anti-Parkinsonian drugs (APD) in Australia from 1995 to 2009. METHODS: We analyzed the Medicare Australia and Drug Utilisation Sub-Committee (DUSC) databases for prescription data for overall APD dispensed use from 1995. We were able to examine prescribing by gender, age, and type of prescriber between 2002 and 2009. Prescriptions were converted to defined daily doses (DDD)/1000 population/day using Australian Bureau of Statistics population data. RESULTS: Dispensed use of levodopa + carbidopa remained steady from 1995 to 2009 (0.76-0.82 DDD/1000 population/day); levodopa + benserazide use increased from 0.34 to 0.55 DDD/1000 population/day. Since 2005 dispensed use of levodopa + carbidopa + entacapone has steadily increased, from 0.03 to 0.10 DDD/1000 population/day. In July 2009 levodopa + carbidopa was the most widely used agent, followed by levodopa + benserazide, then benztropine. Cabergoline increased from 1999, peaked in 2006, and thereafter declined. APD use peaked in males and females aged 60-69 years. Age-adjusted utilization was slightly higher in males than females. CONCLUSIONS: The amount of levodopa dispensed has slowly increased with levodopa + benserazide increasing faster than levodopa + carbidopa. Use of cabergoline fell when pramipexole became available and the risk of ergot-related serosal adverse effects was more widely appreciated. Use of centrally acting anti-cholinergics decreased over a period of time when use of atypical anti-psychotic agents increased.

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.

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.

Awareness of axial spondyloarthritis among chiropractors and osteopaths: findings from a UK Web-based survey.

OBJECTIVE: Chiropractors and osteopaths are important professional partners in the management of axial spondyloarthritis (axSpA). In view of recent advances in diagnosis and treatment, we sought to understand their current knowledge and working practices. METHODS: A Web-based survey was advertised to chiropractors and osteopaths via the Royal College of Chiropractors and the Institute of Osteopathy. RESULTS: Of 382 completed responses [237 chiropractors (62%) and 145 osteopaths (38%)], all were familiar with AS, but only 63 and 25% were familiar with the terms axSpA and non-radiographic axSpA, respectively. Seventy-seven per cent were confident with inflammatory back pain. Respondents routinely asked about IBD (91%), psoriasis (81%), acute anterior uveitis (49%), peripheral arthritis (71%), genitourinary/gut infection (56%), enthesitis (30%) and dactylitis (20%). Eighty-seven per cent were aware of the association between axSpA and HLA-B27. Only 29% recognized that axSpA was common in women. Forty per cent recommend an X-ray (pelvic in 80%) and, if normal, 27% would recommend MRI of the sacroiliac joints and whole spine. Forty-four per cent were aware of biologic therapies. Forty-three per cent were confident with the process of onward referral to rheumatology via the general practitioner (GP). The principal perceived barrier to onward referral was reluctance by the GP to accept their professional opinion. CONCLUSION: Overall knowledge of ankylosing spondylitis is good, but the term axSpA is poorly understood. Specific learning needs include gender preponderance, awareness of acute anterior uveitis and the availability of biological therapies. There is lack of confidence in the onward referral process to rheumatology via the GP.

An Australian Biobank Certification Scheme: A Study of Economic Costs to Participating Biobanks.

Biobanks face increasing demands for research materials of consistent quality, which can be used in collaborative studies. Several countries and some international agencies have made formal efforts to standardize biobank operations and outputs. These include the establishment of best practice guidelines for collection management, and certification programs. Such guidelines and programs increase biobanks' opportunities for participation in high impact research and funding. However, they also impose economic and time costs, which may burden biobanks. This study aimed to estimate the costs of gaining certification and maintaining certification (i.e., committing extra resources to continue standards) for three cancer biobanks participating in a biobank certification program in New South Wales, Australia. To gather cost data for a range of cancer biobanks, we recruited three with different full time equivalent (FTE) staff levels (1.0-3.0), recognizing FTE staff level as an indicator of resources and operating scale. In extended interviews with staff, we gathered biobanks' expected costs in obtaining and annually maintaining certification. The biobank with the highest staff level reported the lowest expected costs in gaining certification, due to the strong prealignment of its present operations with certification requirements. The other biobanks expected higher costs as their operations required greater adjustments. Overall, relative costs of gaining certification were between 2% and 6% of current total annual wage costs. To the authors' knowledge, this is the first such costing study of a biobank certification program. Supplementary Data include the interview schedule that other biobanks may use to estimate their own economic certification costs.

Clinical Trial of MGMT(P140K) Gene Therapy in the Treatment of Pediatric Patients with Brain Tumors.

Gene transfer targeting hematopoietic stem cells (HSC) in children has shown sustained therapeutic benefit in the treatment of genetic diseases affecting the immune system, most notably in severe combined immunodeficiencies affecting T-cell function. The HSC compartment has also been successfully targeted using gene transfer in children with genetic diseases affecting the central nervous system, such as metachromatic leukodystrophy and adrenoleukodystrophy. HSCs are also a target for genetic modification in strategies aiming to confer drug resistance to chemotherapy agents so as to reduce off-target toxicity, and to allow for chemotherapy dose escalation with the possibility of enhanced therapeutic benefit. In a trial of this strategy in adult glioma patients, significant engraftment of gene-modified HSCs expressing a mutant of the DNA repair protein O6-methyl-guanine-methyl-transferase (MGMT(P140K)) showed potential in conferring drug resistance against the combined effect of O6-benzylguanine (O6BG)/temozolomide (TMZ) chemotherapy. The aim was to test the safety and feasibility of this approach in children with poor prognosis brain tumors. In this Phase I trial, seven patients received gene-modified HSC following myelo-suppressive conditioning, but with only transient low-level engraftment of MGMT(P140K) gene-modified cells detectable in four patients. All patients received O6BG/TMZ chemotherapy following infusion of gene-modified cells, with five patients eligible for chemotherapy dose escalation, though in the absence of demonstrable transgene-mediated chemoprotection. Since all gene-modified cell products met the criteria for release and assays for engraftment potential met expected outcome measures, inadequate cell dose, conditioning chemotherapy, and/or underlying bone-marrow function may have contributed to the lack of sustained engraftment of gene-modified cells. We were able to demonstrate safe conduct of a technically complex Phase I study encompassing manufacture of the gene therapy vector, genetically modified cells, and a drug product specifically for the trial in compliance with both local and national regulatory requirements.

The 2018 Revision of the ISBER Best Practices: Summary of Changes and the Editorial Team's Development Process.

An increased need for specimens of reliable and consistent quality for research purposes requires the development of standardized policies and practices for the collection, handling, storage, retrieval, and distribution of specimens and specimen-related data. Providers of specimen resources should strive to incorporate new technologies and state-of-the-science approaches and thus ensure the availability of fit-for-purpose research specimens. Strategies to achieve quality outcomes and performance improvements often include adherence to established standards and implementation of best practices. Although standards represent a rigid set of guidelines that define exactly how a task should be completed, best practices are recommended actions and principles that demonstrate an awareness of standards, solve problems, can be replicated, and work in a given context. Adoption of best practice elements will vary based on the goals and circumstances of a given initiative, and in some instances, may not be possible to implement or may represent an aspirational achievement. In an effort to harmonize the scientific, technical, legal, and ethical issues relevant to repositories of biological and environmental specimens, the International Society for Biological and Environmental Repositories (ISBER) has released the updated ISBER Best Practices: Recommendations for Repositories (ISBER Best Practices). The document provides a comprehensive tool to guide repository professionals in both managerial and technical aspects such as practical details on repository governance, development, and operation; regulatory compliance; and ethical, legal, and social issues relevant to repositories. This summary describes the process for revising the document and summarizes the new topics, updates, and areas of expansion included in the fourth edition of ISBER Best Practices.

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.

Quality and reporting practices in an Australian cancer biobank cohort.

OBJECTIVES: Inadequate research biospecimen quality may adversely impact research translation to clinical practice. Despite the development and endorsement of external quality assurance (QA) programs and biospecimen quality reporting tools, there has been little examination of relevant biobank practices. DESIGN AND METHODS: An online survey was designed to describe the use and communication of QA and quality control (QC) measures within an Australian cancer biobank cohort (n=21), classified according to access policy. Survey questions examined the development and maintenance of Standard Operating Procedures (SOPs), other specific QA and biospecimen QC activities, and communication of biospecimen QC results to researchers. RESULTS: Over three quarters of biobanks utilised regularly-reviewed, best-practice-referenced SOPs, and most biobanks undertook at least one QC activity. Whereas all open-access biobanks (n=11) utilised SOPs and undertook at least one QC activity, these practices were significantly less frequent in restricted-access biobanks (n=10). There were overall low rates of recording the SPREC code, with increased but incomplete recording of Tier 1 BRISQ data. Open-access biobanks were significantly more likely to provide biospecimen QC results to researchers, and to report receiving requests for QC results or additional sample data. CONCLUSIONS: Improved resourcing and education may be required to boost current levels of QA and QC activities and reporting by cancer biobanks.