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.

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.

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.

Certification for biobanks: the program developed by the Canadian Tumour Repository Network (CTRNet).

Two core aspects of the discipline of biobanking are biospecimen quality and good governance. Meeting the demands of both sample quality and governance can be challenging, especially in a resource limited environment. Frequently, differences between biobank processes reduce the ability for cooperative action and specimen sharing with researchers. In the Canadian context, we have made an attempt to identify these gaps and have provided a framework to support excellence, initially for tumor biobanks. The Canadian Tumour Repository Network (CTRNet) was established with funding from the Canadian Institute of Health Sciences (CIHR) Institute of Cancer Research (ICR) to foster translational research through improved access to high quality tumour biospecimens. Consistent with this mandate, CTRNet has focused on the establishment and deployment of common standards to harmonize biospecimen quality and approaches to governance. More recently, CTRNet has implemented a certification program to communicate these standards in conjunction with simultaneous exposure to education focusing on the rationale and foundations underlying these standards. The CTRNet certification program comprises registration and certification steps as two linked phases. In the registration phase, launched in November 2011, biobanks are registered into the system and individuals complete an introductory educational module. In the subsequent certification phase, the type of biobank is classified and assigned relevant educational modules and adoption of relevant standards of practice is confirmed through review of documentation including policies and protocols that address the CTRNet Required Operational Practices (ROPs). An important feature of the program is that it is intended for all types of tumor biobanks, so the scope and extent of assessment is scaled to the type of biobank. This program will provide an easily adoptable and flexible mechanism to communicate common standards through education and address both quality assurance and governance across the broad spectrum of biobanks.

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.

An essential role for MCL-1 in ATR-mediated CHK1 phosphorylation.

Here we report a novel role for myeloid cell leukemia 1 (Mcl-1), a Bcl-2 family member, in regulating phosphorylation and activation of DNA damage checkpoint kinase, Chk1. Increased expression of nuclear Mcl-1 and/or a previously reported short nuclear form of Mcl-1, snMcl-1, was observed in response to treatment with low concentrations of etoposide or low doses of UV irradiation. We showed that after etoposide treatment, Mcl-1 could coimmunoprecipitate with the regulatory kinase, Chk1. Chk1 is a known regulator of DNA damage response, and its phosphorylation is associated with activation of the kinase. Transient transfection with Mcl-1 resulted in an increase in the expression of phospho-Ser345 Chk1, in the absence of any evidence of DNA damage, and accumulation of cells in G2. Importantly, knockdown of Mcl-1 expression abolished Chk1 phosphorylation in response to DNA damage. Mcl-1 could induce Chk1 phosphorylation in ATM-negative (ataxia telangectasia mutated) cells, but this response was lost in ATR (AT mutated and Rad3 related)-defective cells. Low levels of UV treatment also caused transient increases in Mcl-1 levels and an ATR-dependent phosphorylation of Chk1. Together, our results strongly support an essential regulatory role for Mcl-1, perhaps acting as an adaptor protein, in controlling the ATR-mediated regulation of Chk1 phosphorylation.

In vitro anti-proliferative and antioxidant studies on Devil's Club Oplopanax horridus.

Devil's Club, Oplopanax horridus (OH), is a widely used folk medicine in Alaska and British Columbia for treating a variety of ailments including arthritis, fever and diabetes. HPLC profiling shows that numerous compounds are present in the 70% ethanolic extract of OH dry root bark powder. OH extract inhibited K562, HL60, MCF7 and MDA-MB-468 cell growth with the 50% inhibition (IC(50)) estimated at 1/2700, 1/1700, 1/500 and 1/2500 dilutions, respectively. Non-cytotoxic concentrations (