Infra Biobank Norway 2

Transcription

1 Infra Biobank Norway 2 1. Relevance to the call for proposals Biobank Norway (BBMRI.no) was established as a large-scale national research infrastructure for clinical and population based biobanks in 2010 (later referred to as Biobank Norway 1, BN1). It followed the preceding infrastructure for population biobanks, Biohealth Norway and the Regional Research Biobank of Central Norway, which were both initially funded under the FUGE-program The host institutions and coordinators for Biohealth and Biobank Norway, NIPH and NTNU, were actively involved as partners in the establishment of the European biobank research infrastructure, BBMRI.eu (on the ESFRI roadmap since 2008). Later, we have been partners and WPleaders in both BioSHaRE.eu and BBMRI-LPC, representing Norway as observatory member of BBMRI-ERIC from , full member from 2016 and presently leading the Nordic Biobank Network. Biobank Norway was among the first 10 large scale research infrastructures to be listed on the Norwegian roadmap for research. Over the last 4 years, Biobank Norway has increased the number of users exponentially, offering a wide range of well described, richly annotated bio-specimens and corresponding health related data, which has contributed to several hundred research projects subsequently published in a vast number of high-profiled publications. Other deliverables are new and automated storage solutions, new data base solutions, a custom designed LIMS, sample tracking systems and Best biobank Practice. In the present application, we seek funding to consolidate these major achievements, but equally important to improve, expand and develop the infrastructure further (BN2). 2. Vision and scientific goals. a. Biobank Norway shall sustain and strengthen its role as a highly advanced and comprehensive national research infrastructure for health sciences b. Biobank Norway shall enhance the use of biobanks as a basis for excellent research and innovation, and reinforce our ability to participate in international research c. Biobank Norway shall provide internationally competitive biobanking services for basic, clinical, and epidemiological medical research An important objective for all medical research is to discover causes of disease and reveal disease mechanisms with the ultimate goal of better prevention, diagnostics and treatment. Biobanks and population cohorts have been especially effective in the studies of gene/environmental interactions. Currently, the genetic community is systematically evaluating less frequent variants than examined with the initial genome-wide association study (GWAS)- approach, with the hypothesis that low frequency variants (<5% frequency) and rare variants (<1% frequency) will disclose more genes that play a significant role. Recent studies illustrate the possibilities and potential of such a strategy (Holmen Nat genet 2014, Flannick Nat Gent 2014). Fully understanding the gene/environmental interactions requires large, coordinated sets of data, information from population based registries, cohorts and clinical databases, with corresponding biological samples. Health data and biospecimen have up till now been collected from more than 1,4 mill healthy members of the Norwegian population prior to disease development. Since 2010, Biobank Norway has been established as an efficient, unified infrastructure for optimal utilization of these resources and is presently a large consortium with equal partners including the 1

2 four major universities, NIPH, all four regional health authorities and the Cancer registry and biobank. From 2016, we will represent Norway as full member on the management committee of BBMRI-ERIC. Both clinical and population based research biobanks have markedly developed and flourished within our infrastructure with a strong link to associated technology platforms for utilizing the biological samples, including chip-array genotyping and sequencing studies. Our goal is to take the development and utilization of Biobank Norway major steps forward with this proposal combined with our strong national and international networks. In Biobank Norway 2 (BN2), we will specifically prioritize the following areas: New investments. The Janus Serum Bank at the Cancer Registry of Norway (CRN), is a populationbased, nationwide, research biobank containing biospecimens from individuals, of whom have later developed cancer. The serum bank is ideal for the search for novel biomarkers potentially relevant for aetiology, early diagnosis, prognosis and choice of therapy. Today the samples are kept at -25 C in a commercial freezer department, and samples are retrieved manually. There is an urgent need to increase the security, improve the logistics, and ease the workflow of the biobank. By transferring the Janus collection to the new Regional Biobank facility, established in collaboration between NIPH, UiO and South-Eastern Health Authority (HSØ), it is possible to take advantage of existing infrastructure and expertise. The Western Health Authority (HV), is in the process of establishing a new, automated biobank facility, to cater for numerous existing legacy collections and biobank based research projects. Investment cost for an automated -80 storage will be covered partly by BN2 and by HV. These investments will be funded through WP1, but the purchase procedures handled by HV and the CRN Population Biobanks (WP1, WP 4-8). Population biobanks were organized in a separate WP in BN1, focusing on phenotypic identification and recruitment of new biobanks into the BN-network. The two national biobank facilities, already upgraded with 45 mill NOK will be continuously strengthened through BN2 (WP 1 and WP4-8). Further efforts will focus on improved data storage and management of results from studies generating big data sets e.g. genomics, proteomics, metabolomics (WP4, WP7). Prospective clinical biobanks (WP2). After prioritizing a tracking system for existing collections in BN1, the Regional Health Authorities will increase the efforts to build prospective clinical biobanks for future research into some of the most important and common disease categories. Multicentre biobanking (WP3). Based on their broad experience with fresh frozen tissue sampling, WP 3 will be heading a multi-centre initiative to establish a federated tissue biobank, starting with prostate cancer as a pilot project. A custom research data base has been established within the hospital IT-network. The system can be accessed through a secure web-interface, a solution which is currently used by many research groups in various centres. In addition, WP 3 will seek to develop a more efficient solution to the challenge of information transfer between biobanks and health registries, as well as a searchable data warehouse of FFPE pathology samples. National solutions for Bioinformatics, Data handling and Biocomputing (WP 4). By the established interoperability between data resources, we are in a better position to discover biomarkers for disease risk as well as for prognosis. Besides high data quality, state of the art omics-technologies (genomics, transcriptomics, proteomics, metabolomics etc) also depend heavily on advanced biostatistics and bioinformatics methodology, which will be developed in collaboration with the national bioinformatics infrastructure, Elixir. Communication with the donor community (WP 5). There is a need for Norwegian population studies and associated biobanks to facilitate and improve communication with data donors. The Data Inspectorate emphasizes the need to speed up this development in their recent regulatory requirements for population studies. Privacy preserving communication platforms for information 2

3 and feedback to data donors regarding their personal data must provide relevant and comprehensible information. Improved communication with data donors also includes dynamic consent systems to be developed and tested. Biobank registries and inventories (WP 6) build on three major activities, i) the development of an updated Biobank registry ii) a web based, interactive Biobank inventory and iii) to develop tools, competence and infrastructure for faster and improved access to registry data in collaboration with the infrastructure Health Registries for Research (HRR). A biobank inventory will provide researchers with information on where to find the biobanks comprising samples they need for their specific projects and phenotypes/clinical endpoints at interest to apply for access to such material. National platform for sequencing studies (WP 7). There is a pressing need to streamline the sequence analysis of biobank samples and to coordinate the various infrastructures required to exploit the country s biobank resources. We will seek to establish a unified sequencing pipeline to provide the necessary services in a cost-effective way, including a framework for data sharing of sequencing data that handles privacy issues in accordance with national data protection legislation. This would necessitate the need for stronger collaborative efforts between Biobank Norway, the National Sequencing Centre and Elixir. Innovation/industrial collaboration (WP 8). The objective is to develop a national model and framework for systematic management of innovation efforts and industry collaboration tapping into the rich resources of Norwegian biobanks. This also involves exploring possibilities for and obstacles to commercially oriented projects. Common services for Biobanking and ELSI: Biobanking (CS 1). Since the initial establishment of a national biobank infrastructure, there has been a growing awareness and increased knowledge pertaining to all aspects of biobanking, summarized in the recently published, comprehensive document on Best Biobanking Practice. In CS 1, we want to professionalize this valuable competence as a national biobanking service provider, a responsibility shared between several biobanks. In addition, we will develop a scientific platform for research on biobank sample integrity and the quality of biobanking processes. Ethical, legal and social issues (CS 2). The ambition is to build a national network of ELSIcompetence related to biobanking, including the combination of biobank data with information from population surveys, as well as from health registries and other sources. We will provide practical guidance to biobankers on appropriate response to ELSI issues, develop a national approach to participation in the public discussion on ELSI-issues in biobanking and genomics, and develop cooperation with the ELSI common service within BBMRI-ERIC. 3. Status of current research and infrastructures Biobank based research holds a strong position in Norway. Thus, the Research Council of Norway (RCN) has provided substantial funding to biobanks and biobank based research since A long tradition of consent based health surveys with accompanying collection of blood samples, linked to clinical endpoints and phenotypic information from regional and national health registries has created an increasingly valuable resource for scientific use. The well-established practice to store blood samples, as well as fresh frozen or formalin fixed paraffin embedded tissue from hospital patients has also resulted in large collections of material available for research. There is a growing interest for Norwegian cohorts and biobanks, both nationally and internationally, and in close collaboration with other Nordic and European biobanks, we have contributed substantially in numerous international research projects, not only as data providers, but increasingly often in a more active role, or in the lead of various consortia. Innovation based on biobank resources has 3

4 hitherto not been equally well exploited, but the establishment of the publicly owned company HUNT Biosciences, later Lifandis was also a significant step forward (WP8). 4. Description of the Research Infrastructure. Biobank Norway is a mature, well-established infrastructure, integrated in the organization of partner institutions and supported by the latter. It represents a national network with ramifications throughout the entire country, comprising highly competent research groups as well as advanced physical establishments and installations. Biobank coordinators and staff are located in all major hospitals and universities, and storage facilities have been vastly improved throughout. In BN 1, our strategy has been to upgrade two national biobanks (HUNT/NTNU and the MoBa/NIPH) to an advanced state-of-the art quality, including ISO-certification and high-throughput automated procedures through the entire sample handling pipeline. Thus, the HUNT/CONOR biobank was appointed as the European Research Biobank of the year Work packages and common services suggested to be funded in this application are described in detail below. Our request for funding in BN2 will partly be to consolidate the achievements obtained in BN1, but also to expand and enhance the utility of existing biobanks. We will provide necessary services for obtaining and utilizing the data, and we will organize two nationwide Common Services (for biobanking and ELSI). Specifically we will strengthen our efforts for data handling and data storage in existing biobanks. In the clinical biobanks, we have been mostly working with annotation of samples from legacy/existing collections in BN1, and we want to take this further into organizing prospective clinical biobanks in BN2. Research within specialised health care and especially in the university hospitals accounts for a substantial part of the country s health related research portfolio. Clinical biobank material is the basis for at least 50% of this research activity. However, it is often needed to collect specimens from multiple clinical centres in order to attain the number of samples necessary for sufficient statistical power and sample size. Such efforts have yet been limited, with a few successful exceptions. Tissue biobanking will therefore be organized on a national level, as a new activity, based on an already functional multicentre model. The biobank infrastructure is both localized and distributed, and many of the collections may be accessed electronically through a common portal. This will be improved further with an ambition of only one portal for access to information about all biobanks within the Biobank Norway framework. Biobank Norway is well integrated into other national, Nordic and European research infrastructures both for biobanks (previously described) and for IT/informatics (Elixir). Elixir is invited into BN 2 as an active player in several WPs. In WP 4, our need for resources to develop better IT-solutions for data processing and data storage is well described. Already in BN1, systems for sample tracking, databases for questionnaire data and other analyses, and management systems for biobank processes were either purchased (LabWare) or developed as in-house solutions (HUBRIS, EUTRO, Biobanken ) by all participating institutions. These will be further developed and extended as part of WP 4. All locations/facilities/buildings in BN1 were financed by the partner-institutions as in-kind contributions and they will be similarly financed in BN2. Storage facilities for frozen samples, smaller or larger installations/boxes within the room, will be partly funded through BN2, representing a highly valuable upgrade for both Health West and for the Janus Serum Bank at the Cancer Registry. The new - 20 C, semi-automated storage unit for the Janus Biobank will be located within the regional biobank facility established at Myrens (NIPH) in BN1. Om the European level, we collaborate closely with 20 other European countries within BBMRI-ERIC, on e.g. quality issues, IT-solutions, ethics, Large Population Cohorts and organization of clinical biobanks. Different nodes have several parallel activities or work packages, and we frequently 4

5 interact across work packages on a more operational level. This has markedly increased the number of enthustiastic biobankers involved in international collaboration. WP/CS - overview WP1 Project management, Coordination, Investments WP2 Prospective clinical research biobanks WP3 Multicenter biobanking WP4 IT/Biocomputing WP5 Communication with health study participants/data donors WP6 Biobank Registry WP7 National platform for sequencing studies WP8 Innovation/industrial collaboration CS1 Biobanking CS2 ELSI Dedicated Institutional involvement NTNU -all OUS/HMN/HV/HN/CRN HMN/HV/HN/CRN/OUS UiB/UiO/NTNU/NIPH/CRN UiT/NTNU NIPH/NTNU/CRN UiO/NTNU/NIPH/UiB NTNU, UiO, UiT, UiB, FHI, Regional Health Authorities NTNU/- all NTNU -all WP1: Project management, investments Leader NTNU (Hveem), deputy leader: NIPH (Knudsen) WP1 Start date: Jan 2016 End date: Dec 2018 Tot budget: 33,2 mill NOK Participants All Objectives: 1) Management, coordination and development of the organization 2) coordination of Investments Description of work/tasks: 1) Organise leader group meetings and report on Biobank Norway activity to the Research Council of Norway (RCN) and other stake holders 2) Participate actively and according to member status in the European biobank infrastructure BBMRI-ERIC, and other international biobank initiatives 3) Collaborate closely with other Nordic countries management and coordination of the Nordic Biobank Network 4) Organise a national/nordic conference on biobanking in cooperation with WP6 and CS1 5) Communicate actively with the public and biobank donors through our web site and other initiatives 6) Organize a common web portal for access to biobank resources and cohort studies 7) Together with the relevant partner (HV and RCN), organize tender procedures for all major investments planned for BN2. Deliverables : 1) Organize leader group meetings 2) Common Web Portal for access in place 3) Together with WP5, contribute to better researcher-donor-communication on BN web site 4) Represent Norway on BBMRI-ERIC management committee 5) Initiate tender processes 6) Organize biobank conference WP2: Prospective clinical research biobanks Leader: W. Reed (OUS), co-leader: E. Omenaas (HV) WP2 Start date: July 2015 End date: July 2017 Tot budget: 8,5 mill NOK Participants OUS (Reed), HV (Omenaas), HMN (Skogseth), HN (Zykova), CRN (Ursin) Objectives. The sample tracking system achieved in BN1 will be continued. In BN2, high quality, large, prospective research biobanks in the health care sector will be prioritized in such a way as to ensure optimal handling and storage for future research. We will establish a model for diseasespecific prospective biobanks that can be utilized in all health regions, with consensus on SOPs pertaining to sample handling and storage, staff competence, equipment and IT-infrastructure. 5

6 WP2 will adapt and expand on the work from the prostate cancer pilot in WP3, as well as on the implementation of the minimal dataset initiated in BN1 and taken further in WP6. WP2 will cooperate with SKDE (The national service centre for quality registries) to establish a strategy that will help integrate research biobanks with the national quality registries. Oslo University Hospital (OUS) will prioritize three prospective biobanks. The goal is to collect tumour tissue and matching blood samples from the majority of all cancer patients treated at OUS. A brain biobank will collect normal and diseased brain tissue to investigate new molecular markers for specific diagnostic purposes and translational research, including neurodegenerative diseases in the elderly. A biobank for heart diseases will include blood and tissue material from patients with several cardiac entities. HV will establish high quality biobanks for several common and rare diseases. HN will focus on a prospective cancer biobank and biobank for rare haematological diseases. HM will focus on cancer of the breast, colon and lung. Description of work/tasks. 1) Establish project groups for selected disease specific biobanks and agree upon all operating procedures for sample collection, handling/preparation of samples, storage and retrieval. 2) Establish an updatable consent registry and web based biobank donor information system 3) Barcode all samples in the Janus biobank. 4) Display all in-house biobank collections based on minimal common dataset. 5) Implement a common pricing policy (sample handling and withdrawal) for prospective, clinical biobanks Deliverables 1)At least one state-of-the art prospective clinical biobank will be established in at least three university hospitals 2) Display institutional infrastructure instruments for 3) Electronic signature for patient consent 4) Electronic registration of patient consents 5) Web-portal for patients with information on individual participation in research projects 6) Barcoded Janus samples 7) Initiate implementation of Minimal Common Dataset for all biobanks collection WP3: Multicentre biobanking WP3 Start date: July 2015 End date: July 2018 Total Budget: 10,7 mill NOK Participants Lead: HMN (Skogseth) Co-lead CRN(Ursin) HN (Halvorsen) HV (Sviland) OUS (Reed) NTNU (Hveem) Objectives. WP3 will be based on infrastructure and logistics systems already developed, partly in BN1, and used by the Regional Research Biobank of Central Norway (RRBCN). The material already stored ranges from tissue from various organs, blood fractions, and urine to saliva, faeces and synovial fluid. The collections comprise nearly samples from more than persons participating in 42 registered projects. Researchers from 20 institutions in five different countries have real-time access to the web-based biobank database called Biobanken. The existing infrastructure will be developed further into a systematic collection and storage of cancer tissue and associated information from several hospitals and clinical centres, commencing with prostate cancer as a pilot project. An organizational framework will be developed for the decision, description and deployment of standard operating procedures, as well as control measures to ensure compliance with agreed procedures and correction of deviations, in order to secure that the collected material can be used in future research projects in an efficient and reliable way. We will determine how the information can be linked to the clinical registries at CRN within the current legal framework. This will serve as the basis for establishing similar links with other clinical registries in collaboration with WP2. Ethical awareness is crucial and such questions will be handled in collaboration with Common Services ELSI (CS 2). Description of work/tasks. 1)Evaluate and describe ethical, legal and regulatory requirements for this multicentre approach in collaboration with CS 2 2)Develop organizational framework for 6

7 decision, description, deployment, and evaluation of consensual operating procedures for collection, storage and further management of various types of human material and data in multicentre biobanking 3) Establish a system for the acquisition, recording and storage of information about the samples and their donors using a common web-based database solution. The existing solution has to be evaluated, tested and extended in order to be applicable for more centres/hospitals. 4) Evaluate how data can be efficiently exchanged between research projects and the Cancer Registry using existing platforms, within existing laws and regulations 5) Establish a national generic data warehouse for access to FFPE pathology samples through one common portal Deliverables 1) A national advisory group for tissue biobanking, capable of setting up collection of biological material in various hospitals, with common SOPs, and with consensus on evaluative criteria 2) Start-up of tissue collection from radical prostatectomies, in at least 8 different hospital in the four health regions, fulfilling the criterion above, 3) Functional interface between Biobanken and The Cancer Registry for bidirectional transfer of information to be used in cancer research. 4) Data warehouse for easy access to formalin-fixed pathology material by researchers WP4: IT/Biocomputing WP4 Start date:jan 2015 End date:dec 2017 Total Budget: 9,0 mill NOK Participants UiB (lead Lie, co-lead Jonassen), NIPH (Gjessing, Østensen), NTNU (Sætrom, Holmen) UiO (Thomassen, Hovig), CRN (Rounge) Objectives 1) Develop tools for handling of large scale genotype-data 2) Deploy storage and analysis tools within established secured systems 3) Implement methods for gene-environment interactions, incorporation of epigenetic data and parent-of-origin effects, as well as gene and network information. 4) Provide relevant technical and methodological support for researchers. Within months, large scale genotyping-data from at least participants from the MoBa, HUNT and Tromsø-study will be ready for QC and further analyses. This work package builds partly on previous RCN investments (Biobank Norway, ELIXIR, Health Registries for Research and Harvesting biobanks) and solutions will be developed jointly with the ELIXIR Norway infrastructure, benefit from a tight coupling with other Elixir nodes and be coordinated with WP7. We will work closely with established infrastructures on secure data handling at UiO (TSD) and NTNU (HUNT Cloud) to make sure tools are available in these systems. We will deploy known tools for genetic analysis and develop tools with general utility for genetic association studies in biobank-based research. We will also increase capacity for relevant methods support. Subsequently biobanks also provide opportunities for estimation of a range of different types of genetic associations [1, 2]. Haplin is a general tool of analysis that attempts to meet the new computational and scientific challenges represented by new generations of genetic data. A particular strength of the Haplin framework is post-testing for studies of gene by environment (GxE) interactions for all the above-mentioned genetic effects. Relevant environment and biomarker data are available for all major population based biobanks in Norway. This framework will be generalized to epigenetic data and is relevant for studies of personalized medicine. We will build a user friendly environment for Haplin and standard software like PLINK and GeneABEL in secure data systems, organize analysis workshops and courses, and make programs and competence more generally available. The Haplin framework and other tools will be integrated with bioinformatics solutions for variant calling from high-throughput sequencing data that will allow calling of single nucleotide variants, small indels, copy number variations, and re-arrangements. Downstream of Haplin analysis, bioinformatics tools for overlaying called 7

8 variants on genes, gene regulatory regions, and networks will allow revealing genetic affecting particular biological systems or processes. Description of work/tasks 1)Integrate solutions for data access on current IT-systems for secure data-management 2) Integrate solutions for analysis (inc. capacity) on established software 3) Integration of Norwegian driven tools and platforms (Haplin, GenABEL, Galaxy) 4)Further development of Haplin, programming in R. 5) Provide techincal and methodological support, help desk, and arrange analysis workshops Deliverables 1) Make available secure access to genomics data for researchers in the biobank community 2) Make established software available on these platforms 3) Arrange workshops in large-scale data handling and analysis on the available platforms and software 4) Support service help desk WP 5 Communication with health study participants/data donors Participants Stat: Jan 2016 End: Dec 2018 Budget: 4,0 mill NOK WP5: Lead: UiT (Grimsgaard) Co-lead NTNU (Hveem, Solberg) NIPH (Knutsen) Objectives There is a need for Norwegian population studies and associated biobanks to facilitate and improve communication with participants (data donors). The Data Inspectorate emphasizes the need to speed up this development in their recent regulatory requirements for population studies. Privacy preserving communication platforms for information and feedback to data donors regarding their personal data must provide relevant and comprehensible information. Improved communication with data donors also includes flexible consent systems to be developed and tested. In close connection with CS 2 ELSI and other WPs in BN2, with the Dept of Computer Science at the Faculty of Science and Technology Faculty at UiT, and with the Directorate of health, WP5 will develop a web based My page solution where participants in population based studies and data donors to health registries and biobanks can access (i.e. view) her/his registered data in health studies. My page will also include a web solution to update, extend and/or withdraw consent(s) to research. The HUNT Study and the Tromsø Study will be used for piloting My page for study participants. We will build on established web technology and database solutions already developed and partly funded by RCN through Biohealth and BN1. The revised WP5 aligns with developments within the Health Registries for Research infrastructure project. We intend to use as a common national portal for participants in health studies, and a contact has been established with the Directorate of Health. We aim to develop a platform with a flexibility that allows for access to (view) own health data in central health registries as well. The proposed My page tool for communication with study participants will be a demanding and complex development project. A well designed organizational structure for platform management and future development is crucial. Once developed and properly tested we will make the communications platforms accessible for the BBN2-consortium at the portal. Description of work/tasks 1. Develop a My page privacy preserving information platform for personal feedback to data donors, accessed through the helsenorge.no -website. 2. Develop and test various consent solutions for data donors to biobanks and population studies, available for data donors at the My page platform 3. Implement the My page platform for HUNT/NTNU and Tromsø Study/UiT as test cases 8

9 4. Form a sustainable organization around the My page platform Deliverables 1. Privacy preserving information platform for data donors implemented at 2. Dynamic and flexible consent solutions available for biobanks and population studies. WP6: Biobank Register WP6 Start date: Jan 2016 End date: Dec 2018 Total budget: 5,5 mill NOK Participants Lead: NIPH (Knudsen) Co-lead:NTNU CRN HMN (Hveem) (Ursin, Langseth) (Halgunset) Objectives I. To develop a digital and updated biobank registry. NIPH is legally responsible for a National Biobank Registry with information on all established human biobanks in Norway based on information from the Regional Ethics Committees (REC). The registry is currently being modernised and digitalised, with an up-to-date solution scheduled to be finished by the end of This will provide a basis for new biobanks, but information on the historical already existing research biobanks will not be optimally updated. The aim of the Biobank registry is to provide readily available information on all biobanks in Norway, including a characterization of material and identification of the responsible person. II. To develop a web based Biobank inventory. In the Danish Web based biobank registry, detailed information about 15 million biobank samples from 5,8 million Danes can be linked to phenotypic information from a number of national registries. We will develop a Norwegian Biobank Inventory with many of the same functionalities and features, but with a partly different architecture. The user will present requests to a middle ware where data owners (biobanks, registries) will identify the orders and provide the user with updated, de-identified information about sample history and clinical annotation. The concept and underlying IT-structure requires careful attention to data-security and personal integrity. A pilot will be presented for the Data Inspectorate and other stakeholders, i.e. owners of national registries, biobanks and cohorts. Provided acceptance by the Data Inspectorate, a system developer, already funded by a Nordic e-science infrastructure (NIASC) will be affiliated to the tasks of this WP. III. Improved access to registry data. Over the last few month, based on an initiative from the RCN and its Director Arvid Hallén, attention has been drawn to fact that access and linkage to a wide variety of registers in Norway, is hampered by lack of resources, competence and low priorities from the data owners as well as substantial fees to have this done. WP6 is therefore will therefor take on this challenge in collaboration with the HRR-infrastructure to develop tools, competence and infrastructure for faster and improved access to registry data. This solution could very well be established based on the web based biobank inventory model under development in II (see amendment) Description of work, tasks: Biobank Registry. 1) To maximize the research value of the Biobank registry by including updated information on all existing biobanks. 2) To further develop the Biobank Registry and prepare for integration with Biobank Inventory and minimal common dataset from clinical biobanks. Biobank Inventory 1)To develop the data architecture, source codes and security scheme 2)To present the overall concept for the Data Inspectorate and REC for a general orientation and preliminary approval. 3) In collaboration with the Bioinformatics group at the Danish National 9

10 Biobank, we will involve our own bioinformatics resources in programming and development of the system. 4) Improved access to registry data Improved access to registry data 1) Together with Health Register for Research (HRR), and RCN, we will initiate and establish working groups with participants from all major registry owners, both on a technical and strategical level, to find new solutions for better use of registry data 2) Present a first version of a technical solution for data retrieval from multiple registries Deliverables 1) A digital, modernised complete and updated biobank registry 2) Approval from the data Inspectorate and REC for a Biobank Inventory 3) Implementation and testing of a prototype for the Biobank Inventory 4) Go live with the Biobank Inventory 4) Working groups for Improved access to registry data are established 5) A first version of a new IT-infrastructure for fast and secure data retrieval from multiple registries to be presented WP7: National platform for sequencing studies Leader: Undlien, co-leader Sandvik WP7 Start date: Jan 2016 End date: Dec 2018 Total budget: 4,1 mill NOK Participants UiO (Undlien) NTNU (Sandvik/Holmen) NIPH (Knudsen) UiB (Jonassen/Johansson) Objectives. Streamlining the process from biobank sample to sequence analysis A major use of biobanks in research has been genetic research aiming at identifying genetic causes for disease. While this is expected to continue in the coming years, the methods for studying genetic variation are likely to change toward more sequencing based methods DNA sequencing has a number of advantages compared to GWAS, most importantly the ability to detect rare genetic variation often missed by the GWAS arrays. Recent technological advances in high throughput DNA sequencing (HTS) have made the cost for DNA sequencing fall dramatically (recently dropped below 1000 USD/sample), and we thus see the need to prepare for large-scale sequence studies on the Norwegian cohorts. Conducting sequencing studies in thousands of individuals from population based cohorts propose a set of unique challenges both in sample handling, sequencing capacity, protocol adaptations and secure data management and availability in accordance with necessary privacy concerns. In addition, many researchers may rely on expertise in bioinformatics and biostatistics from core facilities to conduct analysis. Thus, there is an immediate need to prepare and streamline this process by coordinate infrastructures and expertize to be able to exploit the country s biobank resources in these type of studies..we will share expertize between our institutions and infrastructures in both large-scale sample handling (HUNT, MoBa, NTNU Genomic Core Facility (GCF), >120,000 samples analyzed on GWAS arrays in 2014/2015), whole genome sequencing (Norwegian Sequencing Centre (NSC) and NTNU GCF, and UiB), secure storage and data management of sequencing data (NSC, TSD, HUNT Cloud), and bioinformatics and biostatistics (NSC, XXX, XXX, Elixir, NTNU Biocore). We will use this knowledge to develop a framework for coordinating all of these services taking a user perspective. Description of work/tasks 1) To coordinate the various infrastructures needed to perform sequence based studies involving the biobank resources of Norway Deliverables 1) A coordinated service pipeline that provides users services in all aspects of sequencing studies in a cost-efficient way. 2) A framework for data sharing of sequencing data that handles privacy issues in accordance with national data protection legislation WP8: Innovation and industrial collaboration 10

11 WP8 Start date: Jan 2016 End date: Dec 2018 Total budget: 4,7 mill NOK Participants NTNU (C. Jonasson) TTOs in Oslo, Bergen, Trondheim, Tromsø (all representatives for universities and hospitals). NIPH Objectives The WP8 main objective is to develop a sustainable national model and framework for innovation and industry collaboration related to Norwegian biobanks. Such a model must not jeopardize the primary goals and the sound operation and future development of Norwegian biobanks. WP8 may partly develop further, the business model developed by Lifandis AS together with HUNT (public ownership), as well as implementation of structured innovation processes in collaboration with the university TTOs. Since the owners of Lifandis AS have decided to terminate the company, the projects initiated by Lifandis will be run by NTNU (the majority owner). NTNU will also take the lead in WP 8. A newly arranged national workshop pointed out several ways forward for innovation and industrial collaboration, but they were all based on a national model, and preferably through HO 21. A political initiative has also been taken through Helse-og omsorgskomiteen to bring this to the parliament. NTNU, through Lifandis has developed infrastructure and essential competence and experience related to industry-based biobank and epidemiology research projects, currently working with several major industry players as well as being engaged with the Expert Center model developed by the BBMRI network. WP8 will involve mapping major Norwegian biobank inventories (build on activities/results from WP6), and explore specific opportunities/obstacles for commercial oriented projects. The overall long term goal is that Norwegian biobanks and related research groups though industry collaboration shall contribute to faster and cheaper development of new drugs and diagnostics, which in turn will lead to earlier diagnosis and better treatment for more diseases Description of work/tasks 1) Allocate/embed a specific resource at major biobank stakeholders to map inventory and ramifications (ethical and legal) for industry collaboration. 2) Define a model for searchable inventory access tools suitable for feasibility studies (together with WP6). 3) Recruit a panel of international senior industry R&D experts to act as an advisory group to provide constructive input as to industry needs/requirements related to biobank based research projects. 4) Define and develop industry relevant marketing material including all Norwegian biobanks, both for industry sponsored research projects and for internal biobank innovation projects. 5) Streamline a TTO collaboration model by establishing a joint forum to secure optimal use of resources, shared industry networks, co-marketing, etc. Deliverables 1) A consensual sustainable national framework for biobank related innovation and industry collaboration. Milestones 1)Establish a formalized BN-TTO collaboration/forum: 2016/1 2016/2 2) Map inventory and corresponding restrictions/opportunities for industry collaboration in CoNor, MoBa and Janus biobank: 2016/2-2016/4 3) Map inventory and corresponding restrictions/opportunities for industry collaboration in other disease specific biobanks (Breast cancer, Prostate cancer, MS, ): 2016/3-2017/2 4) Establish an (annual) industry-bn dialog seminar/forum: 2016/1-2017/4 5) Execute 2-4 pilot industry sponsored projects involving biobanks/cohorts other than HUNT: 2017/3-2018/4 Common Services 1 Biobanking / Best Practices CS1 Start date: Jan 2016 End date: Dec 2018 Total budget: 2,7 mill NOK 11

12 Participants Lead: NTNU Co-lead:NIPH CRN St.Olav OUS (Reed) (Hveem) (Knudsen) (Gislefoss) (Halgunset) Objectives Since the initial establishment of a national biobank infrastructure (BioHealth), the country s competence in biobanking has been steadily increasing. HUNT biobank was ISO-certified in 2011, and appointed the European Research Biobank of the Year The MoBa biobank was also ISO-certified in Oct and is the major player within the Oslo Regional Biobank center. Highly skilled personnel are also employed and trained at several clinical biobanks. Especially at the Janus biobank, sample quality and sustainability studies have been systematically conducted for a number of years. Kristian Hveem, leader of HUNT biobank has been engaged by SSI, Denmark to lead the construction and organization of the Danish National Biobank. In the previous funding period of Biobank Norway, a comprehensive documentation of Best Biobanking Practices has been published on our web site after a huge involvement and contribution by a large number of biobank enthusiasts from all partner institutions. In total, the Norwegian biobank environment represents a greatly valuable biobanking resource that we propose to organize as a Common Service for Biobanking. Description of work/tasks A disseminated service centre for biobanking coordinated by NTNU for the first 1-2 years, a shared responsibility that would circulate among partners. Deliverables Established biobank help desk. Organize disseminated services such as 1) sample handling, 2) quality management, 3) technical solutions, 3) lab ware, 3) DNA and RNA extraction, quality studies 4) LIMS/Data base solutions 5) Biobank constructions/establishments 6) Energy consumption and recycling Common Services 2 ELSI: CS2 Start date: Jan 2016 End date: Dec 2018 Total Budget: 2,9 mill NOK Participants Lead:NTNU UiO (Ljøsne) UiB (Norheim?) UiT(Fjørtoft) NIPH, CRN, (Solberg) HSØ,HV, HMN, HN Objectives: BBMRI-ERIC has established an ELSI (Ethical, Legal and Social Aspects) Common Service, in order to provide solid monitoring of ELSI issues related to biobanks and biobanking, with the task of disseminating results of relevant surveys and studies, as well as ongoing legislation and developments in each country. Each member country is expected to establish a National Node with a National ELSI Representative to participate in the ELSI Common Service activities and to interface with National Institutions, biobanks and BBMRI-ERIC. CS2 will follow up on relevant evolution in legislations/regulations at the National and European level, and organize answers to relevant public consultations to address matters pertaining to biobanking. CS2 will provide background information and practical guidance to biobankers on how to respond to ELSI issues, and give sound advice based on scientific scrutiny and experience in ethical reviews of European or other international projects. In order to accomplish these tasks, the Norwegian ELSI service team will consist of academic ethical and legal experts with special knowledge of the field of biobanking. In particular, CS2 will try to help striking a reasonable balance between the sometimes conflicting individual right to integrity in the fields of medicine and biology on one hand and the rights to social security and services in cases of illness on the other. CS2 will also specifically analyse and advise on how to interpret the Norwegian biotechnology act for biobank research, how to inform biobank participants, and develop policy suggestions for the handling of incidental findings. Description of work/tasks 1) Build a national network of ELSI-competence on biobanking 2) Provide practical guidance to biobankers to respond to ELSI issues. 3) Develop a national approach 12

13 to communication on ELSI-issues in biobanking and genomics 4) Develop cooperation with the ELSI common service within BBMRI-ERIC Deliverables 1) Building and establishing the ELSI-network 2) Establishing a help desk for ELSIissues within Biobank Norway 3) Produce a robust national ELSI-information package 5. Impacts of the Research Infrastructure Medical sciences, both basic, clinical and population based, will benefit from this typemof infrastructure. In addition, the challenges with handling, processing and storage of data will require advanced additional resources to develop solutions which are at present not available. Innovative opportunities lie in the collaboration between Lifandis and other industrial players, in biomarker validation, clinical trials and even looking for new metabolic pathways and new pathogenic mechanisms as a basis for drug development. Especially in studies on gene/environmental interactions and in the search for rare genetic variants, this infrastructure offers unique opportunities based on high-volume biobanking, advanced sample handling procedures, highthroughput analysis, and deep phenotyping of cohorts that have been followed for decades with a rich palette of exposure variables and access to registry data. Top international expertise in the field are already attracted to the research potential in Norwegian biobanks, resting on three significant features, the high-quality biobanks and cohorts, access to data and growing competence on the Norwegian side. We also see that the willingness to fund excellent science based on state-of-the-art biobanks has been prominent, from EU, ERC, NIH, Wellcome Trust, NordForsk and RCN. The Biobank competence build-up in Norway has already proven to be attractive to other countries, both on the technical side, and on in-house logistics, LIMS and IT. In 2013, the entire Norwegian biobank community, published our version of Best Biobanking Practice, available on our web site. This has been widely in use amongst national groups, but also in other Nordic countries indicating a potential leaf role in this field. Biobank-based research encounters many ethical and societal issues that must be handled carefully and with transparency in order to maintain trust. Norwegian biobanks have chosen to be involved in the public debate, but paying close attention to the voice of the donors. To meet challenges related to whole genome sequencing and data-sharing, the HUNT-study decided to inform donors/participants through a personal letter about the nature of these studies, and the opportunity to opt-out. Only 30 participants decided to do so. Norwegian science has definitely been more visible and involved internationally through biobank based research. So far HUNT data/hunt researchers have collaborated on more than 100 publications on population genetics, with > 20%, published in Nature Genetics [3-5]. And the future seems even more promising based on an initiative to do extensive exome-, and genome wide genotyping on more than participants from MoBa and several CONOR cohorts. This has been jointly funded through the RCN Biobank program, ERC-funds, NIH-grants, and institutional contribution from NIPH, NTNU and Univ. of Michigan. Biobanks have indeed been a door opener into numerous high-profiled international research consortia, where Norwegian scientists, through hard work, also have started to take on more leading roles. There is a strong awareness of ethical issues in Norway, which have been educational for international collaborators. In addition, our expertise in phenotypic classifications, and a growing competence in the use of registry data, has been very useful for many international co-workers. 6. Importance of the research infrastructure for various groups On a national level, several hundred collaborators take part in the multiple activities and tasks that are organized by Biobank Norway, ranging from laboratory work, through complicated IT- 13

14 development, research administration and writing up scientific papers. Users and project size. Based on the HUNT biobank only biological material from donors have been used in research projects over the last 5 years, in 2013 and 2014 close to 40 projects and participants annually. Approx 300 ongoing research projects make use of data and material from the HUNT databank and biobank. In the CONOR biobank, DNA form participants from all major Health surveys is stored and actively used by number of researchers. From the MoBa study, on average, samples have been handed out annually. In 2014 and the first half of 2015, genome and exome wide genotyping will be completed on HUNT participants, trios from MoBa and participants from the Tromsø-study. Three of these projects (CVD, diabetes, obesity) are funded with up to 100 MNOK, involving some highly merited international collaborators [6, 7] as well as experienced, merited researchers on the Norwegian side. [3, 8-12] More than 50 new projects within population genomics are expected to make use of these highly attractive data sets over the next three years. Funding from the RCN biobank program has awarded researchers using Biobank Norway with 100 MNOK since A substantial part of a large ERC grant given to prof Pål Njølstad in 2013 will be spent on trios from Norwegian biobanks. Research consortia and institutions like the GIANT, DIAGRAM, FUSION, NCI/NH, IARC, EPIC and ALSPAC are frequent users of Norwegian biobanks, [5, 13-15] Through the previous work of Lifandis, industrial customers are also attracted to Norwegian biobanks, e.g. into biomarker validation, and have showed interest in biobank based RCT in conjunction with the new wave of the HUNT-survey in A service provider such as Illumina has been an active contributor in setting up our genotyping pipeline for large scale, highthroughput genomics studies. Biobanks and population cohorts provide health authorities, politicians and governmental bodies with evidence based research on public health and common, but complex diseases like diabetes, metabolic syndrome/obesity and CVD also being attractive for public sector. Biobanks within Biobank Norway introduced user fees for access to data and biological material as early as Today, this is implemented through all partners. The substantial use of population biobanks ensures an income based on user fees for the HUNT biobank only on 4.5 mill NOK annually over the last 3 years. The total investment in the HUNT biobank facility since 2006, exceeds 100 mill NOK, recently installing an automated -80 C storage facility to hold 13 mill 0.5 ml tubes. The biobank facilities at the Faculty of Health Sciences, University of Tromsø comprise 85 ultrafreezes, that are mainly allocated to large ongoing population studies involved in several national and international collaborative projects. The biobank storage area is located on campus and partially shared with the University hospital of North Norway (UNN). The total biobank facility annual cost is 22.4 MNOK (running cost 19.5 MNOK + personnel costs (3.2 FTE) 2.9 MNOK). The biobank organisation is currently being restructured as a core facility in collaboration with UNN. Today, EUTRO hosts 12 data registries including CONOR data and the Tromsø study ( has delivered data to >250 research projects and is used to administer all (>700) research projects at the faculty. An integrated biobank module is developed with funding from the Biobank Norway consortium, and is now being implemented at the University hospital of North Norway (UNN). The RCN supported project Health Registries for Research will use EUTRO to link and integrate data from Norwegian health registries for research. Norwegian Institute of Public Health are planning to implement EUTRO in 2015 Janus Serum Bank is a unique population-based, nationwide, research biobank containing prediagnostic biospecimens from individuals, of whom have developed cancer. Janus is currently partner of several international and national cancer research consortia that use our infrastructure; i) NCI cohort consortium ii) NCI IARC consortium for Agricultural cohorts, iii) Prostate Cancer Regional Research network (Movember) aim to integrate basic, translational, 14

15 clinical and epidemiological research. The number of samples delivered in different research projects has increased from 2000 in 2012 to 5000 in Currently there are 40 active projects, annually approximately 7 new projects. In HSØ there is an extensive biobank activity in the hospitals. HSØ collaborates with NIPH and UiO through the Regional Biobank, and the storage facility now contains biological material from 37 research biobanks from the regional hospitals. OUS has a total of 700 biobank storage units, with a total cost of 100 MNOK, and an annual cost of 10 MNOK. OUS had in 2013 registered more than 800 research biobanks, with an annual accrue of 100. OUS has currently about 1700 peer reviewed publications annually, of which about 50% involve biobanks. The hospital has a regional support service for research, comprising biobank advisors. OUS has also established a Biobank and Registry Council. 7. Partners. The following 10 partners are part of BN2: 1) Norwegian University of Science and Technology (NTNU, 2) The Norwegian Institute of Public Health (NIPH), 3) Cancer Registry of Norway, 4) The Western Norway Health Authority (Helse Vest), 5) South-Eastern Regional Health Authority (HSØ), 6) Mid-Norway Regional Health Authority (HMN), 7) Northern Norway Regional Health Authority (HN), 8) the Arctic University of Norway, UiT, 9) University of Oslo and 10) University of Bergen Norwegian University of Science and Technology (NTNU) Coordinator of Biobank Norway. NTNU has a 30 year history of conducting population based cohort studies, by organizing the HUNT study (Helseundersøkelsen I Nord-Trøndelag) ( as a longitudinal, health survey in three waves ( , and ) screening approx person above the age of 13. HUNT biobank has been established as a state of-the-art research biobank sharing biological samples from more than individuals with researchers worldwide. HUNT biobank is also responsible for the CONOR biobank, storing DNA from participants from all the major population studies in Norway. HUNT 4 will be conducted in 2014, with an expected budget of mill NOK. More than 100 researchers at NTNU and a simila numbers of international researchers make use of the HUNT study as their primary scientific data resource, 1,5 PEER reviewed papers are published weekly based on the HUNT study and biobank and > 130 PhDs have been completed. NTNU was until Dec 31 st, 2015 the majority owner of Lifandis AS, and will still take the major responsibility for WP8, after the termination of Lifandis (see description of WP8). HUNT research center and biobank is one of two national biobank facilities in Norway, and partner and WP-leader in BioSHaRE.eu and BBMRI-LPC. HUNT/NTNU will also be the coordinator of BN2, leading WP1 and the Common Services on ELSI and Biobanking. The Norwegian Institute of Public Health (NIPH). The NIPH Biobank is responsible for storage of all biological materials collected through MoBa study ( individuals, >4 million samples). The state-of-the art Biobank also manages biological sample repositories from several other populationbased epidemiological studies in Norway, and is one of two national biobank facilities in Norway. The Biobank has more than 25 employees and is in collaboration with OUH and the University of Oslo in the process of establishing a regional biobank collaboration. Laboratories cover approximately 4,500 square feet and the Biobank harbours additionally >15,000 square feet allotted to storage and repository purposes. The Biobank building also contains two fully automated DNA storage facilities, keeping all samples stored at appropriate temperature (-20 and -80 degrees celsius). The NIPH biobank facilities will host the Janus biobank infrastructure, and NIPH will commit and strongly participate in the managing, coordination and organization of BN II (WP 1). NIPH will be responsible of a digital, updated and improved Biobank registry, and will be involved in the design and implementation of a Biobank inventory in conjunction with a web-portal for easy access for 15

16 researchers. Furthermore, NIPH will strongly participate in the development of functional ITinfrastructure, building bioinformatics and biostatistical competence (WP4 and WP7). We will, in close collaboration with other partners, establish common services related to practical, high quality biobanking including ethical and legal aspects. Participating in BN II and further development of the NIPH biobank as a facility for Regional biobanking is a highly prioritized area at the institute and the proposed involvement and responsibilities are in accordance with the NIPH strategy Cancer Registry of Norway The reporting of neoplasms to the Cancer Registry of Norway (CRN) is mandatory by law and CRN has been estimated to be 98.8% complete. The CRN hosts 8 national clinical cancer registries, where the colorectal cancer and prostate cancer registries are more than 10 years old. These registries include clinical data and follow-up information on these patients. The CRN has been involved in research projects and the organization of the Janus Serum Bank operation since it was established, and Janus was completely integrated within the CRN in Presently, the Janus database contains ca cases of invasive cancer. CRN has high expertise in cancer epidemiology and research integrating biobanks and registries, and was part of a large EU-funded Network of Excellence Cancer Control Using Population-based Registries and Biobanks. CRN was responsible for WP 3 (quality assurance registries) where we developed and implementation high-quality operational procedures according to a quality manual in line with international standards [16, 17] Western Norway Biobank Services. The Western Norway Health Authority (Helse Vest) examined in 2013 the status for clinical biobanks and connected infrastructure in the hospitals. The survey revealed a clear need for improved infrastructure and biobank practice. The process concerning by acquisition and implementation of tracing system for biobanks in the region, supported by Biobank Norway , The work building regional infrastructure for high quality handling, storing and easy access to biobank material has just commenced. The Western Norway Health Authority (Helse Vest) will support common regional services, while the hospitals will provide and support its own infrastructure and qualified biobank personnel with substantial institutional support. Common services, made possible by the application and possible funding from Biobank Norway, will provide services to the hospitals and the universities in the region as well as to national and international collaborators co-working with researchers in our region. We support increased participation in common European research infrastructures such as ECRIN, EATRIS and ELIXIR. A basis is common protocols and biobank handling in order to obtain coordination for high quality research, innovation and improved health care in a cost-effective way. A close cooperation with the biocomputing environment in Bergen and WP4 will support and strengthen our biobank output. South-Eastern Regional Health Authority (HSØ) The competence and interest of the region as an active partner in Biobank Norway lies in the biobanking activities in the hospitals. HSØ accounts for 65% of the biomedical research in Norway and biobanks are an essential part of this. HSØ has established a regional biobank facility in Oslo in cooperation with NIPH and is engaged in developing the facility as a regional biobanking service unit, with the University of Oslo as a third part. HSØ was leader of WP3 in Biobank Norway, supported by The Norwegian Research Council , and have finalised the acquisition and implementation of a tracking system in the region. OUS has a central role in developing and supporting biomedical research within HSØ. The hospital has the main responsibility for 11 national quality registries, among these three for heart disease. OUS will lead the work in WP2 Prospective clinical research biobanks, By participating in BN2, OUS sees this as a strategic important step in to the area of personalized medicine and international collaboration. The activities related to BN2 are based on the hospital s core strategic platform. The hospital will provide and support its own biobanking infrastructure and qualified biobank personnel with substantial institutional support. HSØ will contribute so Biobank Norway will reach its goals 16

17 according to protocol and budget, also to assure that the deliverables will be a contribution to national resource after Mid-Norway Regional Health Authority (HMN) has developed an efficient organizational model for the operation and management of hospital-based research biobanks, ensuring that the collected material is optimally treated and utilized for research purposes. We have developed a robust and flexible solution (db) for registration of trial information and results which meet the most stringent requirements for information security and availability, in line with the requirements of the Health Research Act. We have also developed significant expertise in logistics of collection, processing and analysis of tissue samples. All these solutions are developed with a view that it should be easy to implement them in other health regions and at other universities in most countries with sufficient data infrastructure. Presently, 42 major research projects are using human material stored in Biobanken including extensive international cooperation in Europe. Northern Norway Regional Health Authority (HN) The Biobank facilities at the University Hospital of North Norway (UNN) are located at the hospital and on campus at the Faculty of Health Sciences, the Arctic University of Norway, UiT, with 250 square meters of storage space with 72 cells for ultralow freezers, of which 24 belong to Biobank UNN. Access is limited to dedicated Biobank personnel only. All freezers undergo routinely organized maintenance, have continuous temperature log, and are connected to emergency current generator and centralized alarm with 24h on-call security personnel for both UiT and HN. Currently, approximately samples from investigator-initiated research projects are stored in the protected Biobank UNN facilities, in Biobank UiT of which a number of additional samples are collected from prospective community-based cohort the Tromsø Study. The biobank in Bodø is located in the new laboratory department at the Nordland hospital. The research laboratory has a number of research partners nationally and internationally, and receives samples from several external collaborators. REC has approved of a general cancer clinical biobank at UNN. Biobank staff contributed to the development of "Best Biobanking Practice" SOP s. The EUTRO biobank information and management system (BIMS) with tracking information is customized for implementation at UNN and Helse Nord (HN). Sample collection for general prospective cancer research biobank will be initiated in the near future (REC approval obtained). Upgrade of existing facilities with freezers, nitrogen tanks, dry ice access, tissue biobank laboratory is given high priority within new facilities (MH II). Faculty of Health Sciences, UiT EUTRO is a comprehensive database system developed with support from RCN to administer projects, store and retrieve data in large epidemiological studies. EUTRO is integrated with the NESSTAR WebView application ( for viewing and accessing large survey research databases on the Internet. The Norwegian Data Inspectorate has scrutinized and approved EUTRO for secure data storage. University of Oslo's role in this infrastructure Application is focused on WP7 which aims at streamlining the process of sequencing Projects using biobank samples. However, UiO's interests in the BN infrastructure extends far Beyond this. For many of UiO's researchers BN represents an extremely important Resource in their Research. 8. Project management The project coordinator, Professor Kristian Hveem, MD, PhD, is a professor in Clinical Epidemiology and Medicine at the Faculty of Medicine, NTNU and the director of HUNT Biobank, and the National CONOR biobank. Since 2011, he has been the leader of Biobank Norway. He has been instrumental in the establishment of the Danish National Biobank and served as its first Director from , now engaged as scientific advisor. He was a member of the Biobank Infrastructure Committee (BISC) of the Swedish Research Council ( ), is a member of the SAB of BBMRI.se, the SEAB of BBMRI- LPC, and the international steering committee of P 3 G. From 2015 a member of the SAB of the German National Biobank, and since 2013 a senior advisor of China National Gene Bank. From

18 2016, he is leading the Nordic Biobank Network and represents Norway on the management committee of BBMRI-ERIC. He has more than 120 peer reviewed publications and his main research fields are population genetics (CVD) and gastroenterology. Professor and director of the NIPH, Camilla Stoltenberg has been the deputy leader of BN from All WP-leaders and the PIs from partnering institutions will also in the future be part of the BN2 leader group. A full time coordinator, Vegard Marschhäuser has been, and will continue to be the daily administrator of BN1 and the financial contact with RCN. The leader group has met 4 times pr year and all major decisions have been settled through discussions and consensus. BN2 is already a mature and established infrastructure. Each WP will administrate its own activities to fulfil the described milestones and deliverables. Norway is an observational member of BBMRI-ERIC, expected to be a full member as soon as Norwegian legislation allows for this. Karianne Solaas from the RCN is representing Norway in the BBMRI assembly of members. As an observational member, Norway has not been in the position of leading working groups or take on responsibility for Common Services in BBMRI-ERIC. Since 2014, the RCN and Biobank Norway have each covered 50 % of the membership fee. From 2015 and for the coming five years, the membership fee will be covered by BN only. BN1 was funded with 8o mill NOK for the budget period , later extended till July From 2016, the only assets left will be funds set aside for the membership fee of BBMRI-ERIC.. 9. Plan for access and use, data and knowledge management Since 2011, the Biobank Norway web site has been actively used by biobankers from the national and Nordic community, and maintained by our coordinator. Documents related to Best Biobanking Practice are frequently accessed also through our web site. From 2016, one portal for access to biobank samples and to population studies will be established to simplify access procedures markedly. This will have no impact on access rules, they will still be administered and governed by each cohort. Data handling and data storage is described under WP 4, and partly WP 7. WP 6 will provide insight into metadata and anonymized information about availability of samples for various phenotypes. User fees are already well implemented for all population biobanks, and will gradually also be introduced for clinical biobanks. Information about the infrastructure will as before be published on our web site, through presentation at various conferences as well as cohort publications in peer reviewed publications [18-20]. Similar access rules and user fees applies to all. International groups and industry will also have rights to access, in most studies with Norwegian researchers as collaborators. All biobanks and cohorts have a professionalized system with data access committees and a secretariat that can handle requests on short notice. Existing data may be available for research and innovation through data banks organized differently throughout the infrastructure, but based on similar principles: data is stored in secure databases. Issues related to IPR are usually handled by the different TTOs. 10. Work plan, time-schedule and deliverables (milestones/deliverable in yellow.) Please find a more detailed description under each WP above. Administration and Investments Biobanking WP 2 WP no Activities Common Web Portal Donor-communication web site WP1 BBMRI-ERIC management committee Management Organize tender processes Leader group meetings Organize biobank conference Prospective biobanks in 3 health regions Electronic signature, patient consent 18

19 IT Bioinformatics Biocomputing, Innovation Common services Prospective clinical biobanks WP 3 multi center biobanking WP 4 IT- Biocomputing WP 5, Communication WP 6 Registry and inventory WP 7 Sequencing pipeline WP 8 innovation CS Biobanking CS 2 ELSI Routines for tissue and blood sampling Web based patient info system, +WP1 +WP5 Electronic registries for patient consent Barcoded Janus samples (recruitment) Implementation of Minimal data set initiated ELSI- assessment-concept National Advisory Board Recruitment of technical personnel Annual Workshops Interface BB-database and CRN Additional projects, Collection of Blood Database modification at CRN Secure access to genomic data (recruitment) Sofware available on platforms Workshops Support service-help desk Information platform for data donors Dynamic consent solution Digital biobank inventory Approval biobank inventory Go live Biobank inventory Working groups for Improved access to registry data established Technical prototype for Improved access to registry data in place Collaborative agreements Data analysts recruitment Framework for Data sharing policies Industry, BN seminar/forum Initiate Biobank/TTO collaboration forum Map inventor restrictions, opportunities Exec pilot industry sponsored projects Biobank help desk established (recruitment) Disseminated services organized ELSI help desk established (recruitment) Building ELSI network Robust national ELSI info-package 19