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Evolutionary concepts in biobanking - the BC BioLibrary Watson, Peter H; Wilson-McManus, Janet E; Barnes, Rebecca O; Giesz, Sara C; Png, Adrian; Hegele, Richard G; Brinkman, Jacquelyn N; Mackenzie, Ian R; Huntsman, David G; Junker, Anne; Gilks, Blake; Skarsgard, Erik; Burgess, Michael; Aparicio, Samuel; McManus, Bruce M Nov 12, 2009

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ralssBioMed CentJournal of Translational MedicineOpen AcceMethodologyEvolutionary concepts in biobanking - the BC BioLibraryPeter H Watson*1,2,3, Janet E Wilson-McManus2,4, Rebecca O Barnes1,2, Sara C Giesz2, Adrian Png2, Richard G Hegele2,5, Jacquelyn N Brinkman2,6, Ian R Mackenzie2,3,7, David G Huntsman2,3,7,8, Anne Junker2,9,10, Blake Gilks2,3,7, Erik Skarsgard2,10,11, Michael Burgess2,12, Samuel Aparicio2,3,13 and Bruce M McManus2,3,4,6Address: 1Tumour Tissue Repository, Deeley Research Centre, BC Cancer Agency, 2410 Lee Ave, Victoria, BC, Canada, 2BC BioLibrary, Vancouver, BC, Canada, 3Department of Pathology and Laboratory Medicine, UBC, Vancouver, BC, Canada, 4Prevention of Organ Failure Centre of Excellence, Vancouver, BC, Canada, 5Department of Laboratory Medicine and Pathobiology, Toronto, ON, Canada, 6The James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, Vancouver, BC, Canada, 7Department of Pathology, Vancouver General Hospital, Vancouver, BC, Canada Canada, 8Centre for Translational and Applied Genomics, Vancouver, BC, Canada, 9Clinical Research, Child & Family Research Institute, Vancouver, BC, Canada, 10Children's and Women's Health Centre of BC, Vancouver, BC, Canada, 11Department of Pediatric Surgery, UBC, Vancouver, BC, Canada, 12College for Interdisciplinary Studies, UBC, Vancouver, BC, Canada and 13Department of Genetic Pathology, BC Cancer Agency, Vancouver, BC, CanadaEmail: Peter H Watson* - pwatson@bccancer.bc.ca; Janet E Wilson-McManus - JMcManus@mrl.ubc.ca; Rebecca O Barnes - rbarnes@bccancer.bc.ca; Sara C Giesz - pwatson@bccancer.bc.ca; Adrian Png - APng@mrl.ubc.ca; Richard G Hegele - richard.hegele@utoronto.ca; Jacquelyn N Brinkman - JBrinkman@mrl.ubc.ca; Ian R Mackenzie - ian.mackenzie@vch.ca; David G Huntsman - dhuntsma@bccancer.bc.ca; Anne Junker - ajunker@cw.bc.ca; Blake Gilks - blake.gilks@vch.ca; Erik Skarsgard - eskarsgard@cw.bc.ca; Michael Burgess - mburgess@ethics.ubc.ca; Samuel Aparicio - saparicio@bccrc.ca; Bruce M McManus - bmcmanus@mrl.ubc.ca* Corresponding author    AbstractBackground: Medical research to improve health care faces a major problem in the relativelylimited availability of adequately annotated and collected biospecimens. This limitation is creating agrowing gap between the pace of scientific advances and successful exploitation of this knowledge.Biobanks are an important conduit for transfer of biospecimens (tissues, blood, body fluids) andrelated health data to research. They have evolved outside of the historical source of tissuebiospecimens, clinical pathology archives. Research biobanks have developed advanced standards,protocols, databases, and mechanisms to interface with researchers seeking biospecimens.However, biobanks are often limited in their capacity and ability to ensure quality in the face ofincreasing demand. Our strategy to enhance both capacity and quality in research biobanking is tocreate a new framework that repatriates the activity of biospecimen accrual for biobanks to clinicalpathology.Methods: The British Columbia (BC) BioLibrary is a framework to maximize the accrual of high-quality, annotated biospecimens into biobanks. The BC BioLibrary design primarily encompasses:1) specialized biospecimen collection units embedded within clinical pathology and linked to abiospecimen distribution system that serves biobanks; 2) a systematic process to connect potentialPublished: 12 November 2009Journal of Translational Medicine 2009, 7:95 doi:10.1186/1479-5876-7-95Received: 9 April 2009Accepted: 12 November 2009This article is available from: http://www.translational-medicine.com/content/7/1/95© 2009 Watson et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Page 1 of 11(page number not for citation purposes)donors with biobanks, and to connect biobanks with consented biospecimens; and 3)interdisciplinary governance and oversight informed by public opinion.Journal of Translational Medicine 2009, 7:95 http://www.translational-medicine.com/content/7/1/95Results: The BC BioLibrary has been embraced by biobanking leaders and translationalresearchers throughout BC, across multiple health authorities, institutions, and disciplines. Aninitial pilot network of three Biospecimen Collection Units has been successfully established. Inaddition, two public deliberation events have been held to obtain input from the public on theBioLibrary and on issues including consent, collection of biospecimens and governance.Conclusion: The BC BioLibrary framework addresses common issues for clinical pathology,biobanking, and translational research across multiple institutions and clinical and researchdomains. We anticipate that our framework will lead to enhanced biospecimen accrual capacity andquality, reduced competition between biobanks, and a transparent process for donors thatenhances public trust in biobanking.BackgroundIn the past decade, unprecedented progress has beenmade in health research towards realizing the goal of per-sonalized medicine guided by biomarkers and the abilityto match the right preventive or treatment with the rightpatient, at the right time. Key to this progress has been thevarious '-omics' platforms, as well as bioinformatics,molecular imaging, drug discovery, and in the develop-ment of animal models of human disease [1-3]. However,there is now a disparity between the pace of scientificadvances and the successful utilization of this knowledgefor human benefit. This is partly due to the neglect of acritical platform for this path to personalized medicine -the process of securing biospecimens of the necessaryquality, capacity, and level of annotation, and that aretruly representative of diseased populations.BiobanksBiobanks are central to the process of collection of humanbiospecimens for translational research and have contrib-uted to numerous advancements in our understandingand treatment of disease [3,4]. Biobanks are collections ofhuman biospecimens (tissues, blood and body fluids andtheir derivatives collected for diagnosis and/or forresearch projects) and their associated clinical and out-come data. These biospecimens are typically obtainedfrom a subset of the public who become patients in thehealth care system. These patients provide biospecimensduring clinic visits, diagnostic or therapeutic procedures,or at autopsy. The biospecimens accrued by biobanks areprocessed and preserved in a variety of ways to supportdifferent clinical and research uses, including fixation,freezing and live cell banking. Annotation encompassesdocumentation of the biospecimen's composition, as wellas linkage to health data associated with the patient andtheir condition, treatment and outcome. Processed andannotated biospecimens are then released to researchers.This typically occurs through selection of biospecimencohorts from the biobank database using specified criteriato allow a specific research question to be addressed.Biobanks range in design and user, from those whose pri-mary focus is to support clinical health care (clinicalbiobanks, including pathology archives) to those thathave evolved to primarily support research. Researchbiobanks exist in many formats from populationbiobanks to disease-focused biobanks. The latter includeinformal biobanks associated with small and largeresearch studies, basic research disease-affiliated banks,and clinical trial-biobanks. An escalating demand forbiospecimens is resulting in the transformation ofbiobanking from an immature 'cottage industry' con-ducted by individuals, into a complex institutional activ-ity [5,6]. Biobanking has expanded to embrace a range ofspecialized components including frameworks (ethics,privacy, security), equipment (processing, annotation,storage), operating procedures (biospecimen accrual,processing, annotation, storage, release, distribution,tracking), clinical informatics (pathology, treatment, andoutcome data), database structures (donor consent andpreference lists, inventory management tools, querytools), policies (priorities and access processes), eco-nomic models (funding sources, user fees, intellectualproperty), governance models (for strategy and opera-tions), and personnel with specialized roles and training.This has meant that research biobanking, which was oncean activity mostly limited to clinical pathology, has nowevolved largely outside clinical departments as a researchdiscipline. This maturation is also exemplified by the pub-lication of 'Best Practices' by a number of groups [7-10] aswell as the development of biobank data infrastructuresand common data elements [11-13].Bottlenecks in BiobankingDespite the advances of biobanking described above, sig-nificant issues and limitations remain that are restrictingthe impact of translational research. The major issuesinclude the need to increase the quality and standardiza-tion of biospecimens collected, to enhance accrual capac-ity in terms of scale and disease representation, and aboveall, to maintain public trust in these activities. UnderlyingPage 2 of 11(page number not for citation purposes)Journal of Translational Medicine 2009, 7:95 http://www.translational-medicine.com/content/7/1/95these issues is the need to ensure sustainability ofbiobanks and to provide mechanisms for equitable andappropriate access to biospecimens.Quality issues relate to the complications inherent inimposing complex research collection protocols on theroutine workflow of distinct clinical organizations. Theseissues also relate to the difficulty in striking the right bal-ance and appropriate division of biospecimens for bothclinical and research requirements ('tissue ethics'). In par-ticular this division makes it difficult to ensure that repre-sentative components of the biospecimens exist in bothcollections. One example of this difficulty is the low fre-quency with which pre-cancer lesions are captured inresearch biobanks. Variations between biobanks alsoinfluence quality. Even with recent advancement in theway biobanking is conducted, the impact of pre-analyticalbiospecimen variables, such as collection time [14], is nottypically accounted for in translational research.Capacity issues relate to both geographical and temporalgaps in the biobanking process. The geographic gap occursbecause research biobanks have typically developed inhealth centres with an active research focus, not necessar-ily those with the highest volume or diversity of surgicaland pathology services. Temporal capacity gaps arisebecause treatment occurs independently of opportunitiesto engage patients in research. Most biospecimens arise inthe course of clinical treatment at a single location and isoften completed before the relevance of the biospecimento research becomes apparent, diminishing the opportu-nity to harvest biospecimens using specialized researchprotocols. One example is the patient who chooses toenroll in a clinical cancer therapy trial and has a formalin-fixed paraffin-embedded (FFPE) block created for the clin-ical archive. The retrieval of the FFPE archival block for afuture biomarker assay is often a significant logistic barrierbecause it has been consigned to the clinical archive sev-eral weeks before the patient chooses to become involvedin research. Studies requiring a frozen biospecimen areoften impossible because retaining a frozen biospecimenis frequently not part of the standard clinical protocol.Framework issues include inconsistent ethical frame-works, privacy protection efforts and different "businessmodels" between biobanks [15-18]. These issues createuncertainty around accountability to oversight bodies(e.g., ethics boards, privacy offices, and funding agencies)and to the public. This is of particular concern to thosewho donate their tissue and data to biobanks. Thesedonors have the expectation that their donation will beappropriately, equitably, and maximally utilized toachieve better health care. Events relating to biobankingand directly engages health care, research, and a subset ofsociety, it is essential for biobanking to communicate withthese stakeholders and the public at large.Sustainability issues stem from the nature of funding; thelimited scale and the non-systematic resources dedicatedto biobanking [21]. It has been the expectation thatresearch biobanks should be able to conform to the busi-ness models of other core research technology platforms.Funding for core platforms is typically dependent on localresearch strengths, dispersed over short durations, andanticipates short-term sustainability or profit. This isclearly at odds with the need to annotate samples withextended outcome information over many years duringwhich clinical practice and research questions evolve todetermine the use of specific samples. It is also at oddswith the fundamental nature of biospecimens as giftsfrom generous donors for research. Cost recovery strate-gies for biospecimen retrieval, processing, and appropri-ate annotation are emerging but are difficult to deploy insuch a way that ensures biobanks are self-sustainable.Thus, ongoing costs of biobanking need to be addressedas this is now an essential component of research transla-tion.Access issues around biospecimens and their use are seendifferently from the perspectives of donors, biobanks, andresearch users. For donors, it often means having theopportunity to contribute their biospecimen and healthdata to drive research that can address their specific dis-ease. For biobanks, it means access to potential donors toseek their consent to accrue biospecimens. For researchusers, it means finding and obtaining the right biospeci-mens within biobanks and navigating regulatory andoversight processes. Both donors and biobanks face thegeographical restrictions noted above, wherein the oppor-tunity to connect and to donate is unavailable due to lackof a formal biobank at the potential donors' health treat-ment centre. A final issue that contributes to this barrier isthe currently pervasive, pre-operative approach/consentparadigm which limits the opportunities for patients todonate to biobanks.General Solutions for BiobankingOne solution to address the issues of standardization ofquality and capacity is to create networks of biobanks.This idea has stimulated initiatives and networks atregional and national levels including the CanadianTumour Repository Network [22], CaBIG (cancer Bio-medical Informatics Grid) and OBBR (Office of Biorepos-itories and Biospecimen Research) in the USA [12,23],OnCore in the UK [24], CNIO (Spanish National CancerResearch Centre) in Spain [25], and Biobanking and Bio-Page 3 of 11(page number not for citation purposes)in the UK provide concrete examples of the effect of failingto address these issues[19,20]. As an activity that spansmolecular Resources Research Infrastructure (BBMRI) inEurope [26]. Networks enhance biospecimen and dataJournal of Translational Medicine 2009, 7:95 http://www.translational-medicine.com/content/7/1/95standards as well as awareness and access by research ini-tiatives [27]. However, networks and associations ofbiobanks constitute a 'top-down' approach. They do notaddress local biobanking issues and the geographic andtemporal gaps noted above that are critical for quality andcapacity in biospecimen and data accrual.A complimentary strategic solution to networks and asso-ciations of biobanks is a 'bottom-up' approach to connectdonors and biobanks more effectively. Improved connec-tion between donors and biobanks requires developmentof processes within health systems to enable potentialdonors to be referred to biobanks. Currently, manypatients are not offered the opportunity to donate toresearch biobanks despite evidence, including consentrates and donor feedback, demonstrating that this is desir-able and beneficial to patients [28]. Although mostbiobanks do not offer any direct health benefits to thedonor, there is thought to be a psychological benefit anda sense of empowerment from donating biospecimensand data to aid scientific and medical advancement [17].Improvement in the donor-biobank connection requiresspecific tools to enable donors to register their ongoingstatus (e.g., disease recurrence and long-term treatmenttoxicities) and preferences with biobanks. Underlying thisis the need for improved connection with the publicaround the overall activity of biobanking. In the last fiveyears, public awareness of biobanking has grown to thepoint that it has been ranked as a discipline amongst thetop 10 most important ideas that are changing the world[29]. But the public has also been informed that there areassociated risks and perils [30], thus progress in biobank-ing requires public engagement around the governance ofthe discipline [31].Improved connections between biospecimens andbiobanks requires development of processes to allowbiospecimen collection to be conducted in a standardizedfashion, responsive to research protocols, and within lim-its independent of the timing of research consent relativeto the time of surgery or therapeutic procedure. Thiswould require re-integration of the biospecimen accrualcomponent of research biobanking into clinical pathol-ogy. At the same time, the clinical discipline of pathologyneeds to adopt processes for maintaining its clinicalarchives to support the drive to achieve personalized med-icine. Assessment of biomarkers are essential for this driveand this is changing the value of the clinical archive froma reference library to a 'real-time' clinical tool [32-35].Ultimately it might be argued that repatriation of much ofcurrent research biobanking to clinical pathology is thebest long term approach. This would maintain biospeci-mens as a valuable resource located within the appropri-clinical or research purposes to be made on an ongoingbasis.The BC BioLibrary solution for biobankingThe British Columbia (BC) BioLibrary http://www.bcbiolibrary.ca is a 'bottom-up' solution and was designed toaddress issues discussed above. It arose from the desire ofa provincial health research foundation (the MichaelSmith Foundation for Health Research) to create trans-formative health research infrastructure to enhance thenational and international competitiveness of BC's healthresearch community. A library is defined as a collection ofmaterials organized to provide physical, bibliographicand intellectual access to a target group, with a staff that istrained to provide services and programs related to theinformation needs of the target group. Thus, a 'biolibrary'is defined as a collection framework that provides allforms of biobanks and their users (translational research-ers) with access to human biospecimens. A biolibrary dif-fers from a biobank in that its primary focus is limited toacquisition, cataloguing, and distribution of biospeci-mens to biobanks (Figure 1). In contrast, a biobank spe-cializes in its capability for biospecimen processing,annotation with histological and donor health data, andlong-term storage.MethodsDevelopment of the BC BioLibraryThe BC BioLibrary is a framework which consists of 3main components: 1) 'Biospecimen Collection Units',established within clinical pathology departments; 2)patient/donor and biobank/user connections and engage-ment through hospital referral processes and web-basedconsent and inventory catalogues; and 3) public delibera-tion to guide its governance. The framework also includesseveral planned support components including a'Biospecimen Distribution Unit'. The complete frame-work as envisaged is described below, followed by the cur-rent development status.Biospecimen Collection UnitsThe Biospecimen Collection Units (BCUs) embeddedwithin pathology departments comprise trained biospeci-men acquisition personnel (BCU Coordinators) super-vised by the appropriate clinical leader within eachpathology department. Training provided by the BCBioLibrary and its collection of standard operating proce-dures extends the skills of pathologists' assistants andtechnologists with further knowledge surroundingbiobanking, research requirements, protocols, ethics andprivacy issues. The BCU facilitates the triage of biospeci-mens into multiple formats, including formalin-fixed par-affin-embedded tissue blocks, flash frozen or OCT-frozenPage 4 of 11(page number not for citation purposes)ate privacy environment, facilitate accrual, clinical andhistological annotation, and enable appropriate triage formaterial. Collected biospecimens are held in short termstorage and catalogued by logging a unique BC BioLibraryJournal of Translational Medicine 2009, 7:95 http://www.translational-medicine.com/content/7/1/95identification number into the relevant clinical pathologyrecord. Elements of this record are extracted into the BCUinventory database (the 'BCU Catalogue').Patient/Donor and Biobank ConnectionThe consent process relating to biospecimen use forresearch has traditionally involved three distinct steps -permission to contact, the preliminary interview to ascer-tain interest and preferred medium for detailed discus-sion, and the informed consent discussion and agreementitself. The BC BioLibrary, acting as an 'honest broker' ena-bles the key first step, by instituting a process to obtainconsent after the surgery or therapeutic procedure ('post-operative consent protocol'). The BCU enables patholo-gists to routinely harvest and hold portions of biospeci-mens for research, in parallel with the portions ofbiospecimens sampled and assessed for clinical diagnosis.Once diagnosis has been completed and any immediatediagnostic need for these portions has expired, the con-sent status and potential research destiny of these researchbiospecimens can be determined. The BCU facilitates thecontact step by communicating with the responsible clini-cian (the surgeon or their designate such as the medicalharvested, to ascertain if the patient/potential donor willprovide permission for contact. If permission is granted,the BCU can forward the referral to the relevant, REB-approved biobank. The biobank can then deploy its ownconsent protocol or request this service from the BC BioLi-brary consent office. Following completion of the consentprocess, the biobank notifies the BCU Coordinator of theconsent status for any biospecimens that have been col-lected.The status of the biospecimen with respect to the potentialdonor's specific research interests may already be knownthrough a pre-operative consent process, at the time ofharvesting. In this instance the BCU can distribute directlyto a specific biobank. If consent has been withheld by thepatient the research biospecimen is not collected or isdestroyed once this patient decision is known. Alterna-tively, if the patient has not been approached pre-opera-tively by a biobank, the biospecimen can be collected heldby the BCU for a defined period under an approved post-op consent protocol, before its ability to be used forresearch is determined. If at the end of the defined period,the consent decision is unknown (e.g., due to inability toThe BC BioLibrary and its componentsFigure 1The BC BioLibrary and its components. The BC BioLibrary is a framework that lies upstream from biobanks in the cycle that begins and ends with people and leads to their better health. Specifically addressing the aspects of biobanking that involve collection and processing of biospecimens, the components include: 1) the Biospecimen Collection Units which are embedded in the hospital pathology departments and facilitates research orientated biospecimen processing by trained personnel using SOPs; 2) data management infrastructures which enable integration of consent information provided to biobanks with biospec-imens from patient donors; and 3) public engagement processes to allow informed deliberation and input from the public into the governance of biobanking.          	                           ff fi   fl    ffi  ! "  #  $  %  &" ' '  $   "  (   	           	 )  * + ,  -       -   . /  /  , 0 fl12 34 567 8 9   ) ff  : ; < = >    ? @ '  $A B  B  %   C   D E F    F ? $  ? F G      )   H ff  )  1Page 5 of 11(page number not for citation purposes)office assistant) once a potential biospecimen has been make contact with the patient), the biospecimen and allJournal of Translational Medicine 2009, 7:95 http://www.translational-medicine.com/content/7/1/95related data are irreversibly anonymized (Figure 2). Theseanonymized biospecimens may then be distributed toREB-approved biobanks.Biospecimen and Biobank Connection through Web-based Consent and Inventory CataloguesAnother key component of the BC BioLibrary is the devel-opment of an improved linkage between biospecimensand biobanks via web-based catalogues of existingbiospecimens (the 'Biospecimen Inventory Catalogue')and consents (the 'Consent Catalogue').The Biospecimen Inventory Catalogue component isdesigned to provide a list of all biospecimens in short-term storage across different BCUs. This component is stillunder development. It is envisaged that it will be a search-able database for existing biospecimens that are availablefor distribution from the BCUs or alternatively frombiobanks in the community that have an established REB-approved process for request and distribution of theirbiospecimens. The information available in this databasewill contain completely anonymized data: the BC BioLi-brary ID, donor's age at the time of biospecimen collec-The possible status of biospecimens collected by the BC BioLibrary BCU, as determined by the consent linked to the biospec-im n in relation to the time of surgeryFigure 2The possible status of biospecimens collected by the BC BioLibrary BCU, as determined by the consent linked to the biospecimen in relation to the time of surgery. The consent status of biospecimens collected and held by the BCU is influenced by two possible mechanisms for consent: #1) Pre-Operative Consent: If consent is secured pre-opera-tively by a biobank then the biospecimen (green circle) is collected by the BCU and distributed to the biobank as a coded but identifiable biospecimen that can be linked to the patient donor clinical data by the biobank. #2) Post-Operative Consent: If consent is to be sought post-operatively then the biospecimen is collected by the BCU and held as an identifiable biospecimen (orange circle) for a period of up to 90 days (orange lines). During this time the consent status of the biospecimen may change and allow distribution to a biobank as follows: Accomplished - biospecimen (green circle) is distributed as per the procedure fol-lowing a Pre-Operative Consent process. Not accomplished - the biospecimen (grey circle) and all related collection data is ano-nymized and distributed to a biobank (if approved to receive such biospecimens) or destroyed Withheld - biospecimen (purple 1) Pre-Operative Consent 2) Post-Operative Consent90 day periodAnonymizedIdentifiableBiospecimenBiospecimen#1Consent:Accomplished#2Consent:AccomplishedConsent:Not accomplishedC tBiospecimen destroyedonsen :WithheldDay 0 (Biospecimen collected) Day 90Page 6 of 11(page number not for citation purposes)circle) and all related collection data is destroyed.Journal of Translational Medicine 2009, 7:95 http://www.translational-medicine.com/content/7/1/95tion, donor's gender, type of biospecimen and diseaseclassification, and its location and availability. Data willbe linked to a request form directed to the BC BioLibraryor to the biobank housing the biospecimen.The Consent Catalogue component will be designed tomaintain lists which can be populated by each authenti-cated, disease-focused biobank seeking access to biospec-imens that are collected by the BCUs and that are derivedfrom donors enrolled into the biobank. Access to each listwithin the Consent Catalogue is restricted to the originat-ing biobank. The Consent Catalogue will be programmedto establish a link between consented donors entered intothese lists and their corresponding biospecimens collectedin the BCUs. The mechanism for connecting donor con-sent with the associated biospecimens will be by periodicdownload of the Consent Catalogue as an encrypted fileto each BCU computer workstation. Using an unsuper-vised query tool, the BCU inventory database will estab-lish linkage between biospecimens at that BCU andconsented donors within the Consent Catalogue. Allmatches will generate a flag in the BCU inventory data-base as well as a report to enable classification of thebiospecimens collected to date by consent status. Basedon this report the BCU Coordinator will then destroy, dis-tribute, or anonymize and then distribute biospecimensto the appropriate biobank.Public and Biobank Connection through DeliberationMaintaining and improving public confidence is crucial tothe social sustainability of biobanking. Public trust isassociated with many topics: governance, clarity of mis-sion and motivation, and transparency around issues offunding and use for academic and industry applications.The BC BioLibrary provides an attractive focus for inputfrom the public on all topics due to its broad scope anddirect focus on the primary intersection between patientsand biospecimen accrual. The BC BioLibrary has beenlaunched with an initial governance structure designed bybiobanking experts and under the external oversight ofethics committees, privacy laws, and health research foun-dations. However, the intention is to actively seek publicinput into this structure and to evolve by integrating thisinput into the oversight of biospecimen collection. Publicinput is sought through a series of public consultationevents and based on a consensus building approach thatis fostered by deliberative democracy. The focus of theseevents will evolve from discussion of general questionsaround biobanking to more specific discussions aroundthe BC BioLibrary and biobanks and their associated gov-ernance models.Access to Biospecimensdetermine priority of each user application and authenti-cation including documentation of research ethicsapproval (conducted by an institutional REB) to receiveand work with the human biospecimens requested.Although still evolving as the BC BioLibrary expands fromsingle site pilot BCUs into a network, the BC BioLibraryuser access committee is envisaged to comprise represent-atives from BCU sites and the BC BioLibrary managementand executive teams. The committee conducts scientificpeer review scaled to the request and logged through for-mal applications to assign priority for access to BCUs andseeks to ensure feasibility, fairness and accountability.Single site requests are approved at the local BCU level bythe site director, site BCU Coordinator, and the BC BioLi-brary manager. External and multi-site requests are han-dled by the full BC BioLibrary access review committee.All activities are reviewed by the BC BioLibrary Executive.The BC BioLibrary creates a forum to seek resolutions ofcompeting requirements for biospecimens through peerreview and draws from collective experience in managingaccess to biobanks. For those conflicts that persist, a bal-anced consideration through peer review can help to rec-ognize local priorities while also balancing these withdonor preferences and the scientific merit of differentprojects. Most conflicts can be resolved by shared access,division of the biospecimen, or staggered accrual periodsor sites. Another important aspect of user access involvesauthentication of the users' scientific credentials and theethical and privacy considerations. REB review andapproval addresses these aspects and determines whetheraccess is restricted to biospecimens associated withproject-specific consent or can also include anonymizedbiospecimens.Distribution and Backup Storage for BiobanksEach BCU currently transfers biospecimens direct to theuser, but once more BCUs are established, a single portalfor transfer and circulation of requested samples (e.g., acentralized 'Biospecimen Distribution Unit') will be moreefficient. Users may also choose to receive processedbiospecimens and to utilize a range of services andadvanced analytical platforms available through theCenter for Translational and Advanced Genomics con-nected to the BC BioLibrary [36]. Once distributed, theability to properly store and secure frozen biospecimens isthe responsibility of biobank users.ResultsTo prepare for initial implementation of the BC BioLi-brary plan, we began by delineating the functional com-ponents required. A communications plan was developedand a set of key messages derived to articulate compo-nents as they related to five overarching goals. The mes-Page 7 of 11(page number not for citation purposes)Access to the BC BioLibrary requires scientific review (con-ducted by a BC BioLibrary user access committee) tosages were defined as follows: 1) the BC BioLibrary is afacilitator, not a biobank; 2) the BC BioLibrary is intendedJournal of Translational Medicine 2009, 7:95 http://www.translational-medicine.com/content/7/1/95to help all interested BC researchers and educators; 3) theBC BioLibrary helps pathologists streamline and improvebiobanking activities; 4) the BC BioLibrary enhances qual-ity and accessibility of biospecimens; and 5) the BC BioLi-brary contributes to the sustainability of biobanking in BCby developing and upholding the public's trust. We pur-sued this initial 'communication' effort in advance offunctional components to reduce the strong potential formisinterpretation of the objectives and motivation under-lying a new plan around biospecimen procurement fromthe many established key stakeholders. The ongoing needto correct the persistent assumption that biobanking cancontinue as a 'cottage industry' and the misconceptionthat the BC BioLibrary exists to create a single 'BCbiobank' underscores the value of this approach.Implementation began with the establishment of projectteams in 2007 to focus on the three main components ofthe framework: standardization of biospecimens collec-tion and processing ('Biospecimen Collection Unit andTraining' team, 13 members); enhanced communicationbetween the donors, biobanks ('Database and Informat-ics' team, 7 members); and public engagement aroundbiobanking ('Public Engagement' team, 9 members).These teams are managed by an Executive Committee (9members) and the Management team (3 members), withoversight provided by a Governance Oversight Commit-tee (9 members). Through these teams and committeesthe BC BioLibrary is driven by leaders in biobanking andtranslational research across British Columbia, spanningfour major academic hospitals, three health authorities,multiple affiliated academic institutions, and five majorinstitutional biobanks. The latter includes the BC CancerAgency Tumor Tissue Repository (TTR) program [37] andthe affiliated TTR Breast Bank, the Ovarian CancerResearch Program of BC [38], the PROOF Centre of Excel-lence [39], and the James Hogg iCAPTURE Centre[40], aswell as many other biobanks embedded within transla-tional research groups.Each element of the BC BioLibrary has been submitted forREB approval in a stepwise fashion. The first two elementsinvolved establishing a website and a single, pilot BCU inone pathology department. The website served to commu-nicate with stakeholders around all aspects of biobankingand the activities of the BC BioLibrary. Creation of thepilot BCU was essential to provide a working prototypearound which we could engage with the REB and pathol-ogy stakeholders. To date this first BCU has collected over450 biospecimens in an 18 month period. Biospecimenscollected include those harvested from donors who pro-vided pre-operative consent to two local studies, as well asbiospecimens collected under the post-operative consentall aspects of biospecimen harvesting and data capture rel-evant to the BCU, the BCU inventory database ('BCU Cat-alogue'), as well as a web based training curriculum. Theevolution from this single, pilot BCU into a functionalaccrual network has now begun with the recent establish-ment of two additional pilot BCUs at additional hospitalsites and the graduation of the first pilot to a full BCUapproved and capable of supporting multiple biobankusers. The two additional web-based Catalogues (Biospec-imen Inventory and Consent Catalogues) will bedeployed to complete the multi-site biospecimen acquisi-tion capability of the BC BioLibrary.An important element addressed by the BC BioLibrary isthe deployment of a system-wide post-operative consentprotocol. The protocol establishes a maximum time spanof 90 days from the time of surgery for holding a biospec-imen in a BCU. This corresponds to the typical outsidelimits of the period of completion of the diagnosis. Thisduration optimally facilitates the necessary clinical proc-ess for all biospecimens (pre-surgically consented or oth-erwise) by enabling portions of the biospecimen to bereclaimed and processed for clinical purposes if necessaryto complete the diagnosis. The parallel processes forobtaining permission to contact, completing the consentdecision, and assigning consent status to the biospecimenhave also been delineated.The construction of additional components of the frame-work for centralized distribution has yet to begin. How-ever as part of this planning process the BC BioLibraryconducted a survey in 2008 to gauge the need for frozenbiospecimens by BC investigators. The results of this sur-vey showed that over 80% of respondents (n = 55) indi-cated they were not currently satisfied with their ability toperform their research using biospecimens collectedthrough their own institution. Of those, 98% believedthey would benefit from access to biospecimens, with spe-cific requirements for disease-specific (89%) and tissue-specific (77%) biospecimens, collected from more thanone institution within the province. The full implementa-tion of the BC BioLibrary BCUs would allow these needsto be met. In addition a literature survey of over 3000papers reported in cancer research journals at 5 year inter-vals from 1988 to 2008 shows that use has increased 3fold. The mean cohort size in research studies that utilizedtissue biospecimens has changed from approximately 50to 150 over this period.The final and key element addresses public trust. A publicengagement process has been launched with the first twoevents held in 2007 and 2009. The design of these events,the methodology and the composition of the participantPage 8 of 11(page number not for citation purposes)pilot and not linked to an identified study. The pilot BCUhas also been used to develop over 17 SOPs which detailgroups is described elsewhere [31]. Briefly, the first eventinvolved a diverse group of 25 members of the BC publicJournal of Translational Medicine 2009, 7:95 http://www.translational-medicine.com/content/7/1/95in an open-ended deliberation on biobanking. Partici-pants were provided with access to information onbiobanks and then asked to discuss and share theirthoughts, concerns, and perspectives on biobanks. Themajority of participants agreed upon support for biobanksin principle and the need for adequate governance ofbiobanks [31]. The second event built on the first engage-ment and sought specific input from the public on gov-ernance, consent protocols, biospecimen collection, andlinkage to health information. In each area, specific ques-tions were considered such as the best person, communi-cation method, and timing for obtaining consent. Theoutcomes are currently under analysis. The results fromthe public engagement activities has strengthened ourinteractions with the Research Ethics Board, physiciansand researchers as the public's wishes are in line with thevision of the BC BioLibrary.DiscussionBiobanking has historically focused on accrual and anno-tation of biospecimens, but equally critical is the creationof processes for engaging the public before accrual, dis-tributing biospecimens, and cultivating inter-biobank col-laborations. Further efforts towards fostering synergybetween the public and biobanks and associated proc-esses will enhance scientific and technological advance-ment and the translation of discovery to the clinic.The BC BioLibrary is a novel, province-wide strategyaimed at public engagement in biobanking, a commonframework for biospecimen acquisition embedded inpathology departments, and integration of this frame-work with existing biobanks and a spectrum of researchfacilities. The design builds on evolutionary conceptsincluding the repatriation of biospecimen acquisition forbiobanks back into pathology departments and sharedgovernance of these processes.As defined above, a 'biolibrary' differs from a biobank. Abiolibrary focuses on the complexities of connectingdonors with biobanks and on acquisition, cataloguing,and distribution of biospecimens to biobanks. One com-parable example of a biolibrary is the Cooperative HumanTissue Network (CHTN) [41]. The program has developeda prospective biospecimen collection system that is linkedto a wide variety of individual research and biobankrequests. This program is a highly successful frameworkfor support of basic research where the study questionsrevolve principally around issues that do not require out-come data. The BioLibrary also shares elements with theShared Pathology Informatics Network (SPIN) [42],designed to enable indexing, annotation and retrieval ofbiospecimens from clinical pathology archives to certifiedon archival biospecimens. Both models share design ele-ments with the BioLibrary that 'repatriate' components ofbiobanking to clinical pathology.Neither model directly accommodates the consent statusof the biospecimen. The CHTN was developed using thenon-specific surgical consent as a basis for distribution ofanonymized biospecimens with time-of-diagnosis anno-tation. Both the CHTN and SPIN lack components toeffect public engagement. The BC BioLibrary builds onthese models to accommodate informed consent status ofbiospecimens and enable a prospective connectionbetween a biospecimen, the donor's health record, andprospective clinical treatment and outcome data. But per-haps more importantly, the act of communication and thetransaction which leads to the approval to collect andstore a biospecimen linked to personal health data forresearch purposes is critical to the future of biobanking.An example of the acute effect on biobanking when publicconfidence is lost was referred to above [19]. A substantialeffort directed at legal and regulatory reform was thenrequired to restore public and government trust and re-enable continued investment in biobanking [20]. Exam-ples of less obvious effects of denying patients the chanceto make choices and decisions, and with this the lostopportunity to communicate with them around biobank-ing, can be gleaned from the study of organ donation ratesin countries with opt-in and opt-out systems [43]. The BCBioLibrary framework aims to maximize the opportuni-ties for potential donors to be approached by biobanks forinformed consent to participate in research.Although there is a growing body of evidence for the eth-ical acceptability of post-operative consent process [44],many biobanks' and their ethics committees have not yetadopted this more attractive approach. By creating aframework that can act as an honest broker, the BC BioLi-brary facilitates deployment of a systematic post-operativeconsent protocol. The BC BioLibrary can therefore over-come geographic gaps for biobanks and facilitate donoropportunities that would not otherwise be possible.Current regulatory requirements for biobanking havebeen developed to protect the interests of the public.However, the implementation of regulations to addressprivacy issues that were developed without biobanking inmind [45] has required adaptation to biobanking proc-esses and poses serious challenges to the pace of researchand financial burden to the researchers. At the same time,it is not clear if the range of different interests or the prior-ities of the public is well served by current regulatoryregimes. The establishment of a process of public involve-ment in parallel with a new process for biospecimenPage 9 of 11(page number not for citation purposes)research projects and investigators. In contrast to theCHTN, this system and its concept was focused principallyaccrual has been essential in gaining trust from profes-sional colleagues around issues such as the motivation ofJournal of Translational Medicine 2009, 7:95 http://www.translational-medicine.com/content/7/1/95the accrual network and in providing assurance toResearch Ethics Boards that the concept and operation ofthe BioLibrary will be acceptable to the public. Publicinput, fostered through deliberative democracy events,will help us to devise trustworthy governance and to pro-mote wider public understanding of biobanks [46]. Publicinvolvement will therefore contribute to the social sus-tainability of the project.ConclusionThe BC BioLibrary framework is designed to maximize theopportunity and capability of injecting high quality, accu-rately annotated biospecimens into all forms of biobanks.This framework addresses geographical and temporalissues that currently limit the capacity and capability ofbiobanking. In the process, it provides improved opportu-nity for oversight of biospecimen usage, standardizationof consent and collection processes, and equity inbiospecimen distribution to biobanks. Perhaps mostimportantly, by creating a common shared infrastructure,this framework reduces competition between biobanksand offers a transparent process for donors to participate,thereby enhancing public trust and providing an opportu-nity for public involvement in designing optimal govern-ance of biobanking.AbbreviationsBC: British Columbia; BCU: Biospecimen CollectionUnit; OCT: Optimal Cutting Temperature compound;REB: Research Ethics Board; SOP: Standard OperatingProcedure; MSFHR: Michael Smith Foundation for HealthResearch.Competing interestsThe authors declare that they have no competing interests.Authors' contributionsThe authors' contributions to this manuscript are reflectedin the order names are shown. PHW and JEM supervisedall aspects of this study and contributed to the manuscriptpreparation. ROB and SCG participated in the manuscriptpreparation. All authors contributed to the conception ofthe ideas embodied here and to the development andimplementation of this study. All authors read andapproved the final manuscript.AcknowledgementsThe BC BioLibrary is funded by a MSFHR Technology/Methodology Plat-form grant.References1. Towbin JA, Bowles NE: The failing heart.  Nature 2002,415:227-233.2. Strausberg RL, Simpson AJ, Old LJ, Riggins GJ: Oncogenomics andthe development of new cancer therapies.  Nature 2004,3. Topol EJ, Murray SS, Frazer KA: The genomics gold rush.  Jama2007, 298:218-221.4. Korn D: Contribution of the Human Tissue Archive to theAdvancement of Medical Knowledge and the Public Health.Research Involving Human Biological Material:Ethical Issues and PolicyGuidance 2000, II:1-30.5. Morente MM, Fernandez PL, de Alava E: Biobanking: old activityor young discipline?  Semin Diagn Pathol 2008, 25:317-322.6. Ginsburg GS, Burke TW, Febbo P: Centralized biorepositoriesfor genetic and genomic research.  Jama 2008, 299:1359-1361.7. Dhir R: Prostate cancer biobanking.  Curr Opin Urol 2008,18:309-314.8. Troyer D: Biorepository standards and protocols for collect-ing, processing, and storing human tissues.  Methods Mol Biol2008, 441:193-220.9. ISBER: 2008 Best Practices for Repositories Collection, Stor-age, Retrieval and Distribution of Biological Materials forResearch.  CELL PRESERVATION TECHNOLOGY 2008, 6:3-58.10. US National Institutes of Health-National Cancer Institute: NationalCancer Institute Best Practices for Biospecimen Resources.2007.11. Mohanty SK, Mistry AT, Amin W, Parwani AV, Pople AK, SchmandtL, Winters SB, Milliken E, Kim P, Whelan NB, et al.: The develop-ment and deployment of Common Data Elements for tissuebanks for translational research in cancer - an emergingstandard based approach for the Mesothelioma Virtual Tis-sue Bank.  BMC Cancer 2008, 8:91.12. Welcome to the caBIGTM community Web site   [https://cabig.nci.nih.gov]13. Unified Medical Language System Metathesaurus fact sheet[http://www.nlm.nih.gov/pubs/factsheets/umlsmeta.html]14. Barnes RO, Parisien M, Murphy LC, Watson PH: Influence of evo-lution in tumor biobanking on the interpretation of transla-tional research.  Cancer Epidemiol Biomarkers Prev 2008,17:3344-3350.15. Auray-Blais C, Patenaude J: A biobank management modelapplicable to biomedical research.  BMC Med Ethics 2006, 7:E4.16. Busby H: Biobanks, bioethics and concepts of donated bloodin the UK.  Sociol Health Illn 2006, 28:850-865.17. PRIM&R Human Tissue/Specimen Banking Working Group: Reportof the Public Responsibility in Medicine and Research(PRIM&R) Human Tissue/Specimen Banking WorkingGroup, Part I Assessment and Recommendations.  2007.18. Gibson E, Brazil K, Coughlin MD, Emerson C, Fournier F, Schwartz L,Szala-Meneok KV, Weisbaum KM, Willison DJ: Who's minding theshop? The role of Canadian research ethics boards in the cre-ation and uses of registries and biobanks.  BMC Med Ethics 2008,9:17.19. Hall D: Reflecting on Redfern: What can we learn from theAlder Hey story?  Arch Dis Child 2001, 84:455-456.20. Retained Organs Commission: Retained organs.  Bull Med Ethics2002:8-11.21. Riegman PH, Morente MM, Betsou F, de Blasio P, Geary P, the MarbleArch International Working Group on Biobanking for, Research B:Biobanking for better healthcare.  Molecular Oncology 2008,2:213-222.22. The Canadian Tumour Repository Network   [https://www.ctrnet.ca/]23. OBBR Office of Biorepositories and Biospecimen Research[http://biospecimens.cancer.gov]24. onCore UK   [http://www.oncoreuk.org]25. CNIO   [http://www.cnio.es/es/index.asp]26. Welcome to BBMRI Preparatory Phase   [http://www.bbmri.eu/]27. Riegman PH, Dinjens WN, Oosterhuis JW: Biobanking for inter-disciplinary clinical research.  Pathobiology 2007, 74:239-244.28. Malone T, Catalano PJ, O'Dwyer PJ, Giantonio B: High rate of con-sent to bank biologic samples for future research: the East-ern Cooperative Oncology Group experience.  J Natl CancerInst 2002, 94:769-771.29. Park A: 10 Ideas Changing the World Right Now- #8Biobanks.  Time 2009.30. The Economist: Medicine's new central bankers.  The Economist2005.Page 10 of 11(page number not for citation purposes)429:469-474.Publish with BioMed Central   and  every scientist can read your work free of charge"BioMed Central will be the most significant development for disseminating the results of biomedical research in our lifetime."Sir Paul Nurse, Cancer Research UKYour research papers will be:available free of charge to the entire biomedical communitypeer reviewed and published immediately upon acceptancecited in PubMed and archived on PubMed Central Journal of Translational Medicine 2009, 7:95 http://www.translational-medicine.com/content/7/1/9531. Secko DM, Preto N, Niemeyer S, Burgess MM: Informed consentin biobank research: A deliberative approach to the debate.Soc Sci Med 2009, 68:781-789.32. Holland NT, Smith MT, Eskenazi B, Bastaki M: Biological samplecollection and processing for molecular epidemiologicalstudies.  Mutat Res 2003, 543:217-234.33. Dowsett M, Dunbier AK: Emerging biomarkers and new under-standing of traditional markers in personalized therapy forbreast cancer.  Clin Cancer Res 2008, 14:8019-8026.34. Early Breast Cancer Trialists' Collaborative Group: Tamoxifen forearly breast cancer: an overview of the randomised trials.Lancet 1998, 351:1451-1467.35. Slamon D, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL:Human breast cancer: correlation of relapse and survivalwith amplification of the HER-2/neu oncogene.  Science 1987,235:177-182.36. CTAG-Analytical & Laboratory Services   [http://www.phsa.ca/AgenciesAndServices/Services/PHSA-Labs/About-PHSA-Labs/CTAG.htm]37. BC Cancer Agency Tumor Tissue Repository   [http://bccancer.bc.ca/RES/TTR]38. Ovarian Cancer Research Program of BC   [http://ovcare.ca/research/platforms.php]39. PROOF Centre of Excellence   [http://www.proofcentre.ca/]40. James Hogg iCAPTURE Centre Biobank   [http://www.icapture.ubc.ca/what/what_registry.shtml]41. Cooperative Human Tissue Network   [http://chtn.nci.nih.gov/]42. Shared Pathology Informatics Network   [http://www.cancerdiagnosis.nci.nih.gov/spin/]43. Organ Donation Taskforce UK: The potential impact of an optout system for organ donation in the UK: an independentreport from the Organ Donation Taskforce.  2008.44. Hewitt R, Watson PH, Dhir R, Aamodt R, Thomas G, Mercola D,Grizzle WE, Morente MM: Timing of consent for the researchuse of surgically removed tissue: is postoperative consentingacceptable?  Cancer 2009, 115:4-9.45. Key Issues   [http://www.priv.gc.ca/legislation/02_07_01_01_e.cfm]46. Secko DM, Burgess M, O'Doherty K: Perspectives on engagingthe public in the ethics of emerging biotechnologies: fromsalmon to biobanks to neuroethics.  Account Res 2008,15:283-302.yours — you keep the copyrightSubmit your manuscript here:http://www.biomedcentral.com/info/publishing_adv.aspBioMedcentralPage 11 of 11(page number not for citation purposes)

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