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.

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.

Permission to contact (PTC)--a strategy to enhance patient engagement in translational research.

UNLABELLED: Improving patient recruitment and consent to participate in clinical studies is an important issue. The process of consent involves three steps: patient referral for contact, the preliminary interview to determine patient interest, and the informed consent discussion. We hypothesized that putting the first step of the consent process into a 'Permission to Contact' (PTC) platform would improve patient engagement, would improve the efficiency of the other steps of the process, and would be acceptable to diverse patient groups. METHODS: To test this hypothesis, four PTC platforms were established in three types of outpatient health clinics (cancer, cardiac, maternal health) in different British Columbia health centers. Each began as a research project where clinic personnel were engaged, clinic flow processes were mapped, and a design for each PTC was derived by consensus. All patients at these clinics were asked for 'permission to be contacted for future research purposes.' Patient approach and permission response rates were assessed and operational costs were estimated. RESULTS: Overall permission rates were high for all projects, but ranged from 94% of 'cancer' patients to 80% of 'congenital heart' patients who were approached (p<0.0001). Sustainability was demonstrated by stable enrollment levels after several years, and ongoing costs averaged $25 (range $12-$39) for each 'permission' across all four platforms. CONCLUSIONS: A PTC platform is a feasible mechanism to engage patients in research programs such as biobanking. It is well supported by clinic staff and receives high engagement and acceptance from patients. Patient-approach rates vary in different clinics, likely due to both clinic and PTC process factors, but this strategy provides an efficient means of engaging patients in research and sets the stage for enhanced enrollment into translational research programs.

Impact of a Permission to Contact (PTC) platform on biobank enrollment and efficiency.

The consent process involves three steps; referral for contact, preliminary interview, and informed consent discussion. We propose that the efficiency and frequency of the consent process for individual biobank related projects increases when the referral for contact is conducted by an independent "Permission to Contact" (PTC) platform within a health research organization. A PTC platform established at our center in 2007 obtains "permission to be contacted about future cancer research" from approximately 1200 patients annually. With ethics board approval, the British Columbia (BC) Cancer Agency's Tumour Tissue Repository (TTR) deployed a post-procedure consent protocol designed to obtain initial referrals from the PTC platform. This protocol was initially deployed for breast and gastrointestinal (GI) cancer patients (48% of patients), and later expanded as an option for all patients. We examined the impact on biobank accrual over a 4-year period spanning implementation of the post-procedure protocol. Within the first 2 years, while deploying an existing pre-procedure consent protocol, the TTR received, on average, 38.5 referrals/month, and consented 36.5 patients/month. Over the next 24 months, referral and consent rates increased to 68.5/month and 45.6/month, respectively, while operating both pre-procedure and post-procedure protocols. This represents a significant increase in overall referrals (1.78 fold) and consented patients (1.25 fold). For breast and GI cancer patients, referrals and consents, increased even further (2.4 and 1.6 fold, respectively). Overall, the consented/declined/unknown decision rates in the first period were 95.3%/1.2%/3.5% (n=918 approached patients), while rates in the second period were 86%/2.3%/11.7% (n=1272 approached patients). Overall, consent process costs fell by 14% per case. Patient engagement can be positively influenced by connecting a biobank with a PTC platform enhancing efficiency in obtaining consent, which is a key determinant of tumor biobank costs.

An online tool for improving biospecimen data element reporting.

Detailed documentation of the experimental materials and methods is essential for the validation of scientific papers. Human biospecimens are increasingly utilized as materials in cancer research and information about the biospecimens used is a component of this documentation. We hypothesized that previously reported biospecimen data are inadequate for accurate replication and/or validation of a substantial proportion of studies. To examine this issue, we analyzed biospecimen reporting in a representative cross section of publications over the past 12 years (1998, 2004, 2010) in the journals, Cancer Research (CR, n=46) and Clinical Cancer Research (CCR, n=73). We assessed biospecimen data in relation to the standards outlined as the Tier 1 recommended data elements from the Biospecimen Reporting for Improved Study Quality (BRISQ), in addition to ethics criteria. These data elements encompass features of biospecimens influenced by the patient, medical procedure, and biospecimen acquisition, handling and storage processes. Analysis found that while there was a significant increase in the reporting of ethics board approval status (p<0.008) and name of the ethics board (p<0.0001), there were no significant differences between these journals or over this period in reporting other biospecimen-related data elements. Of the 15 Tier 1 data elements assessed in CR and CCR, the data elements commonly obtained from the "Clinical Chart" (8/15 elements) were significantly better reported than elements that would typically be obtained from the "Biobank" (p<0.0001). Our findings demonstrate that reporting of biospecimen-related data elements has been incomplete. As one part of the solution to this issue, we propose the use of an online data-elements reporting tool (www.biobanking.ca) by biobanks. This BRISQ Report tool aims to help biobanks provide the relevant biospecimen-related data as a structured report, and to promote its inclusion as supplementary material in publications to improve the quality of future research studies.

Biospecimen use correlates with emerging techniques in cancer research: impact on planning future biobanks.

The average cohort size for tissue biospecimens used in cancer research studies has increased significantly over the last 20 years. To understand some of the factors behind changes in biospecimen use, we examined cancer research publications to characterize the relationship between specific assay techniques and biospecimen formats and products. We assessed a representative cross section of 378 publications in the journal Cancer Research that used tissue biospecimens, selected from 6 intervals between 1988 and 2010. Publications were categorized by biospecimen utilization, format type (Frozen, Formalin-Fixed Paraffin-Embedded, and Fresh), product type (RNA, DNA, Protein, Cells, and Metabolites), and types of research techniques performed. There was an increase in average biospecimen cohort size (p=0.001); relative use of Formalin-Fixed Paraffin-Embedded biospecimens (24%-68%, p<0.0001); and the proportion of techniques assaying RNA products from biospecimens (Frozen and Fresh formats, p<0.05), from 1988 to 2008. However, these trends have not continued and there has been no further increase from 2008 to 2010. While specific techniques such as 'tissue microarray' analysis appear to have driven some changes in format requirements, there is an overall trend towards techniques requiring RNA products across all formats of biospecimens in basic cancer research. Since pre-analytical variables influence gene expression (RNA levels) more than gene structure (DNA sequence), recognition of these research trends is important for biobanks when deciding priorities for the optimal preservation format and annotation of biospecimens.