Operational plan 2015

Transkript

1 Operational plan 2015

2 Welcome to the 2015 Operational plan for BBMRI.se. The year 2015 will be a transition from a preparatory, project-oriented pilot phase to a more customer-oriented phase with established, routinely functioning Service Centers. The overall aim of the 2015 Operational Plan is to enable a clear working plan for how BBMRI.se services should be offered during the next 8-year period The European Union (ESFRI) has established common evaluation criteria for research infrastructures, with these four being of critical relevance for BBMRI.se: concrete and credible plans for construction and operation including costs and financing over the whole life cycle of the project; scientific impact and scientific relevance for the respective scientific area in the updated context; is it a real distributed Research Infrastructure or rather a network or a research project? Social and economic impact including innovation potential and possible cooperation with industry; In the Strategic Meeting of the scientific leaders of BBMRI.se on 7 th November 2013, two major changes for the future strategy of BBMRI.se were agreed upon: -To as far as possible transition to operational Service Centers that focus on providing services to customers. -To abandon the more project-oriented administrative structure of BBMRI.se with Work Packages (WP). These changes were further discussed with the scientific leaders and university representatives during the spring of 2014 as well as with the BBMRI.se Scientific Advisory Board (SAB). The advice from the SAB was that, in order to build on what has been achieved and because many other countries are looking to what Sweden is doing in this field, the transition to Service Centers should be made in a manner that allows continuation of the achievements made in the old WP structure. During the development of the Operational Plan for 2015, it became apparent that different initiatives of BBMRI.se had reached different degrees of maturity. In some instances, transition to an operative Service Center infrastructure with concrete and credible plans for operation including costs, user fees and other financing is expected to be accomplished during In other instances- particularly in fast-moving areas- additional preparatory work is required, which is intended to be performed using so-called strategic supportive actions. Some highly successful initiatives, notably our Support to Healthcare-based Biobanking and our Information Technologies Service Center are prioritized for future work, but are considered to as yet have too small critical mass to be launched as separate National Service Centers. For the time being, these services will therefore be continued as Services directly offered by BBMRI.se management. Finally, there are also some areas in the biobanking field where it is clear that a national initiative is needed but where more discussions with the stakeholders will be required. 2

3 In these areas, we have added to the operational plan that BBMRI.se during 2015 will engage in discussions regarding which ways forward that may be possible. A particularly important strategic area is our collaboration with healthcare biobanking. The healthcare system has for many decades been storing huge numbers of biospecimens and the systematic biobanks in e.g. clinical laboratory medicine are one of the most important infrastructures for medical research in Sweden. BBMRI.se has already invested in equipment that has been deposited in healthcare-based biobanks all over Sweden. We aim to continuously expand this important part of our activities. Another important goal for BBMRI.se is to strengthen the role of Sweden in the building of the European biobank infrastructure BBMRI-ERIC. BBMRI.se is the Swedish national hub of BBMRI ERIC. In the written interim evaluation of 11 National Research Infrastructure supported by the Swedish Research Council (2012) it was mentioned in the conclusion that BBMRI.se played a fundamental role for the European BBMRI, which would be unthinkable without the Swedish input. Our aim is to further support our input to the European development, by a strategic building of the Swedish capacity in this area. The European Commission has made the following recommendation for the continued development of the biobanking infrastructure in the European Union: BBMRI was awarded ERIC status in November The BBMRI-ERIC focuses on securing and providing access to a key resource of hundreds of biobanks distributed in the EU for the advancement of personalised medicine and disease prevention. BBMRI has the potential to significantly improve competitiveness of health-related industries, such as the pharmaceutical industry, diagnostics manufacturers, and the biotech industry as well as vendors of biobanking related products. There is currently no infrastructure like BBMRI-ERIC outside of Europe, giving Europe a striking competitive advantage. The key next steps to boost and accelerate the implementation of the main European bio-banking and biomolecular resources RI and prepare its functioning and services are: to organise national biobanks and the details of precisely what each country will offer in terms of data and services, and then combine these efforts into a coherent project plan for the European layer; to increase discoverability and access to data by setting up infrastructure, standards and tools for data sharing in a common central software and data framework whilst protecting privacy, and harmonise data and IT across biobanks; to fully develop access procedures and services for researchers; to fully develop a strategy and ensure solutions to the ethical, legal and societal issues related to access to personal data, and involving all relevant sectors to enhance the connection between basic research through to the clinical application; take steps to continue expanding BBMRI s membership. In addition it is recommended that BBMRI should start to test the concept of common services using rare diseases as an example. This will in involve (1) access to high quality 3

4 human biological materials as a prerequisite for research on rare diseases; (2) an online, dynamic, searchable catalogue of samples collected in rare diseases biobanks and also employed in omics studies; (3) harmonisation and quality control of registries, biobanks and research databases in rare diseases; and (4) an Expert Centre on ethical, legal and social issues as well as regulatory issues. The strong Swedish role in the application for a European Service Center for Ethical, Legal and Societal Issues (ELSI) on biobanking (where the BBMRI.se National Service Center for ELSI issues at Uppsala University will be one of 4 European hubs) is a prime example of how our strategy to support the European development in the biobank-based research infrastructure has been successful. Stockholm Joakim Dillner Acting Director, BBMRI.se 4

5 Contents BBMRI.SE NATIONAL SERVICE CENTER FOR SAMPLE MANAGEMENT... 8 BACKGROUND... 8 OVERALL GOALS FOR WORKSTREAMS AND GOALS... 9 BBMRI.SE NATIONAL SERVICE CENTER FOR ETHICAL LEGAL AND SOCIETAL ISSUES (ELSI) IN BIOBANKING ETHICAL AND LEGAL GUIDANCE BASED ON SOUND RESEARCH CONSTRUCTION OF INTERNATIONAL STANDARD DOCUMENTS CONTRIBUTING TO AND LEARNING FROM INTERNATIONAL COLLABORATIONS AND CONFERENCES THE ETHICS BLOG BBMRI.SE NATIONAL SERVICE CENTER FOR ANALYSIS TECHNOLOGIES AND REAGENTS EXPERT CENTRES INFRASTRUCTURAL RESEARCH ON PREANALYTIC VARIABLES AND SAMPLE QUALITY BIOBANKING ANALYSIS RESOURCE CATALOGUE (BARCDB) TECHNOLOGY NETWORKS AND COORDINATION WITH OTHER INITIATIVES THE MOLECULAR METHODS (MOLMETH) DATABASE BBMRI.SE ACCESS AND COHORT ENRICHMENT SERVICE CENTER(S) TO FURTHER DEVELOP A QUALITY ASSURANCE SYSTEM TO BE APPLIED ON BIOBANK PROJECTS AND THEIR INTERACTIONS WITH REGISTRIES OMICS STUDIES WITHIN BBMRI.SE COORDINATION OF BIOBANK INFRASTRUCTURES IN SWEDEN TO ESTABLISH NEW WORLD LEADING INFRASTRUCTURES IN SPECIFIC AREAS EXTENDED COOPERATION WITH NATIONAL AND INTERNATIONAL BIOBANK NETWORKS ON PUBLIC HEALTH ISSUES WITH THE IDENTIFICATION OF SUCCESS STORIES MANAGEMENT ACTIVITIES OF THE BBMRI.SE COMMUNICATION PLAN BBMRI.SE SERVICES FOR SUPPORT TO HEALTHCARE-BASED BIOBANKING INFORMATION TECHNOLOGY SERVICES SUSTAINABILITY, FINANCING, FUNDRAISING & STRATEGY STRATEGIC SUPPORTIVE ACTIONS APPENDIX APPENDIX APPENDIX APPENDIX APPENDIX APPENDIX APPENDIX

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7 BBMRI.se Service Centers A Service Center is offering a defined set of services to researchers and other stakeholders for whom the use of biospecimens could be advantageous. The Service Center has concrete and credible plans for operation including costs, user fees and other financing. Furthermore, the Service Center must have a scientific leadership that can prioritize the development of services to achieve a maximum scientific impact and scientific relevance for the respective scientific area in a continuously updated context. The business plan of the service center should include a strategy on how to maximize the social and economic impact of the services, including the innovation potential and possible cooperation with industry; The Service Center is not merely a network or a research project. Finally, the Service Center must operate in accordance with the ethical and moral values of BBMRI.se. For 2015, the following BBMRI.se Service Centers will provisionally be launched: -BBMRI.se National Service Center for Sample Management -BBMRI.se National Service Center for Ethical, Legal and Societal Issues on Biobanking -BBMRI.se National Service Center for Analysis Technologies and Reagents -BBMRI.se Service Center for Southern Sweden -BBMRI.se Service Center for Access and Cohort Enrichment

8 BBMRI.se National Service Center for Sample Management Background Professional biobank service facilities have become an essential part of modern medical research. Research needs high quality samples in statistically relevant numbers and organised in a systematic, standardised and traceable way. Core biobank services include collection, processing, storage and withdrawal of human samples, and extraction of high quality DNA at high throughput. Interest is growing in more advanced services, such as RNA extraction (including micro RNA) and preparation of viable cells. Several biobank facilities also provide professional advice on matters such as law and ethics (eg informed consent processes), sample quality and data management. Previously (as recently as 10 years ago), research projects resolved their sample needs individually, wasting time and money, and losing any opportunity for beneficial standardization and comparability. In some cases quality of the research materials was compromised. Since health care is based on the results of research, it is in the patient s interest that research is based on material of a consistently high quality. Sweden seems to have been the first country to adopt a more concerted approach to biobanking, with early efforts starting in the Swegene/WCN national biobanking program already in Upon formation of BBMRI.se there was an explicit desire to avoid duplication by running a joint national biobanking service. A majority of BBMRI.se resources would go to pilot operations for creating a national biobank facility to provide unified service to customers from all over the country. The facility would focus on efficient storage and withdrawal to support researchers. This is detailed in the original application. The project would be conducted through a strategic collaboration with KI Biobank, which had the necessary knowledge and skills needed for the introduction. It was stated in the application that funding from VR should be phased down by the end of the initiative, when the business would be self-supporting and able to enter a more operational phase. An evaluation of the pilot phase of the National BBMRI.se biobank facility was requested by the Board of BBMRI.se on 19/9, During the period of biobank facilities have been built up in most of the teaching hospitals in the country, enabling faster freezing of samples to improve quality. Local sample collection with high quality is thus becoming more possible today. The remaining national largescale needs are mainly capacity for large-scale storage and efficient and large-scale withdrawals. Overall goals for 2015 The overall goal in the 2015 plan is to determine the most valuable and credible long-term role for the Service Center, and take the first steps in implementing this. The pilot phase was intended as a basis for building a national facility where researchers and stakeholders from all over the country can use the services, and this remains an important principle. As the first phase of BBMRI.se ( ) ends it is clear that the technical and operational concept of the national large-scale sample handling facility has been fully met. Large-scale 8

9 sample collection and processing operations have been put in place, and are now in routine use, serving over 40 distinct research projects from all over the country and many with a national span of sample collection. Efficient data systems have been developed. High-throughput DNA extraction from blood and saliva has become a routine and high quality service (with > DNA extractions performed so far). High-throughput withdrawal has been established, with one advanced dynamic store (-20C, for half a million samples) already in operation and another (- 80C for 3 million samples) under implementation. The facility has already performed > sample withdrawals for research analyses. Efficient sample retrieval from a single facility is thus helping to alleviate one of the most important bottlenecks in biobank-based research. The researchers that have used these BBMRI.se services have published (during 2013 alone) nearly 70 peer-reviewed articles. The work behind these achievements has been made in accordance with the annual operation plans, which in turn are based on the original 5-year work plan in the 2009 approved application to the Swedish Research Council. Much of the 2014 operation plan has been achieved, but several key areas remain to be completed, and these will become part of the 2015 operational plan. They are also in accordance with the overall goal for the BBMRI.se National Service Center for Sample Management. Workstreams and goals The following workstreams and activities form the 2015 operation plan for SSB: A. Sustainability Increase the level of cost-recovery for the services. At the end of 2015, the service center should have arrived at a 100 % coverage for the resources required for the customer services. The basic cost model envisaged includes 3 parts: 1) Basic costs (costs that would have to be paid also if there were no customers and no development work). Financing from the host university will be sought. 2) Development costs. Many biobanks put as much as half of all costs on development, as the field is changing rapidly and continuous development is required to ensure that efficient, updated and competitive services are offered. Financing from external sources will be sought. Collaboration with other Service Centers nationally and internationally will both reduce these costs and facilitate the development. A specific example is the work package on concerted development of National Biobanking Facilities included in the EU FP7 project BBMRI- LPC, where the BBMRI.se National Service Center for Sample Management is a partner. 3). Resources used for customer services. These will be paid entirely (100%) by Users Fees. The procedure used for pricing and accounting will follow the EU rules for provision of services such as these. Implement an organizational structure that will ensure that customers, stakeholders and all other interested parties will more readily recognize when BBMRI.se national services are provided. 9

10 B. Basic Infrastructure (= continuous improvement of continuous service) Complete the biobank IT architecture redevelopment started in 2014 Establish RNA extraction as a service (assuming there is a first customer during 2015) Complete rebuilding of the current facilities to accommodate the new dynamic store, an LN2 facility, a DNA clean-room and increased sample storage C. High throughput sample withdrawal further development Complete the installation, test and validation of the -80C dynamic store (specified and ordered in 2014) Redevelop the retrieval processes for new operation with even higher throughput D. Collaboration. Continue a joint project with the National Service Center on Molecular Analyses and Reagents on pre-analytical quality factors, in order to definie meaningful and measurable quality parameters (and using a dedicated sample collection for sample quality) Participate in the collaborative project SCAPIS plus (also called Wellomics ) that will apply high throughput ( -omics ) analyses to define sample quality and wellbeing of donors. Continued joint development of national large-scale biobanking services together with other national biobanking service facilities in the EU project BBMRI-LPC Run a training course in how to use biobanks for research (follow-up on our first, successful course given in 2013) 10

11 BBMRI.se National Service Center for Ethical Legal and Societal Issues (ELSI) in Biobanking The overarching goal of this Service Center is to develop and promote a coherent and concise concept of good ethical practice in biobank research based on a correct and constructive interpretation of legal requirements pertaining to Swedish, European and International Law. For this end, we have recruited top scholars working in the fields of biobank ethics, research ethics, public law, administrative law and European law. Due to this gathered expertise we have besides contributing to the creation of a sustainable Swedish infrastructure for research that is ethically sound also attracted substantial interest from several international networks using biobanks and health data for research, including the support of the new BBMRI-ERIC and BBMRI-LPC structures. This, and new developments together with the pharmaceutical industry and collaborations with USA, Australia and Canada will further accelerate the output from the ELSI center during Ethical and legal guidance based on sound research Background Ethical and legal guidance is provided on regular basis to individual researchers, biobank systems consortia, and pharmaceutical industry e.g. SCAPIS, LifeGene, EpiHealth, UCAN, Novartis, GSK, Janssen and AstraZeneca. This guidance is based on the state of the art knowledge about ethical and legal aspects of biobank and registry research, and on sound research published in leading international and Swedish scientific and scholarly journals. Mission Our mission is to promote biobank- and registry-based research that is efficient with regard to increasing biomedical and epidemiological knowledge for the benefit of future patients while safeguarding integrity concerns and ethical and legal standards of this practice. Goals and deliverables Ethical and legal advice on a continuous basis to scientists and biobank systems Publications in good quality journals are planned regarding the following subjects: Dissemination and adaption to Swedish context of a recently published Charter of principles for sharing and access to biopecimens and data. Analysis and suggested balance of the risk of re-identification versus the need to identify individuals ethical aspects of patient unique identifiers. Analysis of how incidental findings in biobank related research should be managed. Results of an empirical survey of ethics review of biobank-related applications Broad consent versus Dynamic consent pros and cons Broad consent for future research (with NIH Bioethics dept) Attitudes to integrity concerns among patient populations in Sweden, in collaboration med Myndigheten för Vårdanalys. 11

12 Edited book : Ethics, Law and Governance of Biobanking in the international context Analysing and follow-up the current drafting of a new Data protection regulation in the European Union Legal analysis of the premises for bio banking in the EU with special focus on informed consent, finding of the applicable law and relevant actors (book, Lind & Reichel) Ethical and legal analyses of a proposed Swedish participation in the IMI-project EHR4CR (Electronic Health Records for Clinical Research) A particularly important activity will be to analyse the proposed new European Union legislation for protection of personally identifiable data. The analysis will investigate the legal basis of the new proposed rules and the consequences different decisions are likely to have on the possibilities to perform medical research. Time plan The publications will be published throughout Project group Mats G. Hansson, Professor of biomedical ethics, Uppsala University Jane Reichel, Associate Professor of Administrative law, Uppsala University Anna-Sara Lind, University lecturer of Public law, Uppsala University Deborah Mascalzoni, PhD, Researcher, Uppsala University Pär Segerdahl, Associate Professor of philosophy and editor, Uppsala University Heidi Howard, Uppsala University Jennifer Viberg, PhD-student in bioethics, Uppsala University All are associated with The Centre for Research Ethics & Bioethics. Construction of International standard documents Background Concrete practical guidance is needed on questions related to informed consent, sharing & access to data and biorepositories and tha handling of incidental findings. Since efficient biobank research implies colaboration across borders this guidance need also be applicable in different national contexts. We will in WP7 provide standard documents regarding these issues. WP7 has also submitted a tender for an ELSI-Common Service of BBMRI-ERIC together with other European node representatives. Mats Hansson will be one of four co-directors. Mission To provide researchers with relevant documents for ethics applications and for collaboration that will ease the process for them while acknowledging their own responsibility to think through the ethical and legal aspects of their research. The ELSI-Common Service will have the following missions: 1. Monitoring mission : provide solid monitoring of ELSI issues related to biobanks and biobanking based on state of the art and deep knowledge of relevant applicable ethical and legal 12

13 frameworks; 2. Policy mission: follow up relevant evolution in legislations/regulations at the European level and organize coordinated answers to relevant public consultations and other possible intervention to address joint matters for the biobanking community on the European level; 3. Advising mission: build conclusions and advise on a sound scientific/academic basis and experience in ethical reviews of European/international projects; 4. Help-desk mission: provide updated background information and practical guidance to biobankers to respond to ELSI, especially in relation to the exchange of human samples and data for research use in Europe ( help--- desk ---format); 5. Dissemination mission: ensure the dissemination of results of relevant surveys and studies toward the various audiences; 6. Tools oriented mission: organize tools and services to address ELSI related to biobanks and biobanking by building on already available tools and generating new ones if necessary; 7. Experience sharing mission: organize sharing and exchanges regarding ELSI between BBMRI-ERIC members; 8. Education mission: set up training and education on ELSI related to biobanks and biobanking; 9. Ethics check mission: provide an ethics check of research proposals submitted to BBMRI- ERIC for their compliance with the BBMRI Work Plan and Statutes and with the European Commission research ethics framework. Goals and deliverables Standard documents will be developed as follows: Charter with principles and template for DTA/MTA Charter with principles and template for informed consent, through a web-based version called Consent Shaper. Preliminary version of template for the management of incidental findings Project group Mats G. Hansson, Professor of biomedical ethics, Uppsala University Deborah Mascalzoni, PhD, Researcher, Uppsala University Jennifer Viberg, PhD-student in bioethics, Uppsala University Pär Segerdahl, Associate Professor of philosophy and editor, Uppsala University Contributing to and learning from international collaborations and conferences Background The researchers working in the Service Center are engaged in several international networks, give lectures and participate in international conferences. Through this Swedish experiences can be disseminated to a wider group of concerned scientists as well as policy makers, and lessons 13

14 can be learned that are of relevance to BBMRI.se. Mission To base research, practice and guidance in ethical and legal matters pertaining to biobank based research on the best available international standards as well as contributing to raising this level of standards. See also on ELSI-Common Service above. Goals and deliverables Based on the international recognition of the research group as centre of international top quality its members are involved in the following established networks and projects: BT-Cure, an IMI-funded collaboration with 33 European partners addressing biobank and registry based issues in autoimmune diseases where WP7 is working with ethical and legal issues. RD-CONNECT, an EU-7th framework project on Rare Diseases with Hans Lochmüller, Newcastle as coordinator where WP7 will work with ethical and legal issues. BBMRI.LPC, an EU-7th framework project with BBMRI.fi (Markus Perola, Helsinki) as coordinator where WP7 will work with ethical and legal issues. EURO-TEAM, an EU-7th framework projects with Christopher Buckley, Birmingham as coordinator where WP7 will work with ethical and legal issues. BIOBANK-CLOUD, an EU-7th framework project on how to manage large quantities of biobank data in an efficient and secure way where WP7 will work with ethical and legal issues. Resource Center for Laboratory Diagnostics, with Joakim Dillner as coordinator. COST Action IS1306: New Speakers in a Multilingual Europe: Opportunities and Challenges, on biobanking Industry Pharmacogenomics Working Group International Pharmaceutical Privacy Consortium NIH Bioethics Department P3G, McGill University, Canada BBMRI Italy (ELSI group) Telethon Scientific Advisory Board, Italy National Comitato delle Regioni for the drafting on a National Law on Biobanking Italy ELSI IGES (ELSI board of the International Genetic Epidemiology Society) European Academy of Bolzano, Italy Advise to the IMI-project EHR4CR If applications for two new Horizon 2020 projects are successful we will work with prevention through cancer screening and risk assessments in colorectal cancer. Project group Mats G. Hansson, Professor of biomedical ethics, Uppsala University Jane Reichel, Associate Professor of Administrative law, Uppsala University 14

15 Anna-Sara Lind, University lecturer of Public law, Uppsala University Deborah Mascalzoni, PhD, Researcher, Uppsala University Heidi Howard. Uppsala University Pär Segerdahl, Associate Professor of philosophy and editor, Uppsala University Jennifer Viberg, PhD-student in bioethics, Uppsala University All are associated with The Centre for Research Ethics & Bioethics. The Ethics Blog The Service Center has also published an ethics blog where a large focus is placed on biobank issues. Pär Segerdahl, philosopher and science writer, is the editor of this blog that is available both in Swedish and English. The basic mission is to be proactive regarding ethical issues related to biobank and registry research based on sound research with regard to the ethical and legal questions. The ethics blog went public in November 2011 and will continue during A publication with selected blog posts will be published. 15

16 BBMRI.se National Service Center for Analysis Technologies and Reagents Among the central roles for BBMRI.se are the tasks to ensure broad access to state of the art and beyond state of the art techniques and reagents for biospecimen analysis, and to promote interoperability of data across studies and biobanks. A continuously updated network has been established linking centres/platforms and facilities across Sweden, which provide access to relevant technologies for measuring and imaging nucleic acids, proteins, metabolites, etc. By ensuring that advanced, and in some cases unique and emerging methods, are put to early and efficient use with high-quality biobank samples, this activity will promote both scientific progress and commercial application by biotechnology, diagnostic and pharmaceutical industries. Some expected medical and exploitable benefits include the discovery of new disease biomarkers and drug targets through large-scale and or novel molecular technologies, in addition to a generally enhanced understanding of disease mechanisms. Expert Centres Background According to the vision of the EU BBMRI ERIC (ERIC = European Research Infrastructure Consortium), Expert Centres should be designed to provide a framework of laboratories where public resources including biobank samples, together with expertise and technologies from academia and industry, can be integrated to promote collaborative research by performing analyses of samples in the country of origin under internationally standardised conditions. The laboratories comprising these Centres will carry out analyses of human biological samples using latest technologies and make the primary data available to academic groups for research or to industry where they may be used in product development. The intention is to provide access for users to a broad spectrum of scientific, medical and technological expertise related to biobank samples, and at the same time reduce or avoid the need for direct sample shipment to users. The BBMRI ERIC has proposed that a network of linked Expert Centres be established to perform precompetitive (early stage) research and data generation using biobank samples; an emphasis on partnering with industry is expected to evolve into a novel, not-for-profit, public/private partnership model. The Centres will initially be established at a national level, with coordination between activities at different Centres. They will be characterised by providing up to date or emerging new technologies, IT solutions and bioinformatics support, cost efficiency, a high level of standardisation, professional quality management, flexible solutions for generation of IP, confidentiality, and ethical and legal compliance. Expert Centres are also seen as excellent breeding grounds for commercial start-up companies, exploiting findings and getting off the ground more quickly by availing themselves of the samples, technologies and expertise available. Sweden is excellently placed to become a leading player in a network of Expert Centres, through its technologically advanced laboratories, such as SciLifeLab, and through BBMRI.se, This network will be developed in conjunction with the EU BBMRI-LPC (Large Population Cohorts) project, designed to encourage the use of biobank resources in Europe, 16

17 where Uppsala University and Karolinska Institutet are partners. Mission To work together with SciLifeLab to establish the functioning for the first Swedish Expert Centre. Goals and Deliverables Liaising with SciLifeLab and others for establishing an Expert Centre for biobank analysis Uppsala University (represented by Dr Joakim Galli and Professor Ulf Landegren) is a partner in the BBMRI-LPC project, including in a workpackage dealing with establishing a network of Expert Centres (WP3), and in another workpackage, with Karolinska Institutet, for development of technologies for DNA and protein analysis (WP9). In relation to BBMRI.se, an important link can be created to the LPC consortium by participating in the establishment of the Swedish Expert Centre(s). The initial focus will be on the SciLifeLab with its comprehensive range of state-of-the-art technical facilities, including advanced genomics, proteomics and metabolomics platforms. Discussions are held with Mathias Uhlén and Kerstin Lindblad-Toh Dr Maria Sörby, Uppsala Site Director, and Dr Fredrik Sterky, Stockholm about how to establish SciLifeLab as an Expert Centre with efficient interfacing to biobank activities in general and to BBMRI.se. This will also require discussions with interested parties from industry about how to best facilitate access to results and develop useful relationships between the publicly funded and private sectors. Infrastructural Research on preanalytic variables and sample quality Background Preanalytical factors of relevance for biospecimens - conditions of collection, processing, storage and distribution - can significantly alter the molecular composition and consistency of biobank samples. Even apparently small procedural changes can significantly affect experimental outcomes, and hence the ability to produce reproducible scientific results. Once a sample is collected, it may take on new characteristics depending on how it is handled. Such changes may result in inaccurate determinations of the molecular and physical characteristics of samples. Every attempt should be made to minimize the effects of handling on biospecimen integrity. This includes not only the temperature and timing of biospecimen processing, but also such considerations as the size and volume of the biospecimen that will be stored for future use. It is increasingly clear that to achieve consistent, harmonised services there is a need to focus on the preanalytical processes used by the service providers. Optimal use of biobank samples depends on identifying the most suitable sample formats for each analysis technology as well as determining how samples should be treated before analysis, including comparability, reproducibility and minimised risks of analytic bias. This should in turn be consistent with recommended standardisation included in Biospecimen Reporting for Improved Study Quality, BRISQ (Moore et al., 2011), and NCI Best Practices for Biospecimen Resources ( 17

18 Mission Our aim is to contribute to harmonisation and establishment of guidelines for the preanalytical phase of sample handling in collaboration with other initiatives. We will initiate and coordinate research projects to optimise the analyses of biobank samples, such as (i) promoting research on collection/storage methods such as choice of tubes, additives, quality standards and SOPs in relation to the analyses to be performed and (ii) development of high-throughput methods to enable analysis of thousands of biobank samples. Goals, Deliverables and Time plan Plasma/serum sample handling for proteomics analyses A pilot project in the field of proteomics is ongoing in the current BBMRI.se WP4, in collaboration with WP6 (Drs Gunnel Tybring and Mark Divers), SciLifeLab Uppsala (Dr Masood Kamali-Moghaddam) and the SME Olink. The aim is to identify and determine the effects of preanalytical variables important for proteomic studies on plasma and serum, e.g. variables of storage vessels, temperature and time from needle to freezer which should be observed to retain good protein quality. Furthermore, we hope to identify markers that could be used to assess the quality of previously stored samples, taking into account published marker proteins. The proximity extension assay (PEA) developed at Olink technology is being used for analysis, with a pilot study due for completion in Q Plasma/serum sample handling for Metabolomics With similar aims as above, we also perform a metabolomics study using GC-MS technology. The data analysis is performed at SLU Umeå (Drs Thomas Moritz and Linus Malm). Tissue fixation In collaboration with the EU project SPIDIA, coordinated by Qiagen, we are investigating PFPE (PAXgene paraffin-embedded) as an alternative tissue fixation method to FFPE (formalin-fixed, paraffin-embedded), which could be better suited for analysis of DNA, RNA and proteins from tissue samples. In situ RNA analysis is performed by the padlock method and protein analysis will be evaluated by the in situ proximity ligation assay. While a number of different tissues have been analysed and promising data have been recorded, we need to confirm the results using a further set of tissues. Protein and gene expression studies on the cytology biobank Discussions are ongoing with BBMRI.se WP3 (Prof Joakim Dillner and Dr Nasrin Persqvist) to start a research project on samples from the cytology biobank newly established within WP3, involving cell samples from a cervix screening programme. The project is intended to show the usability of this biobank for research in various omics fields, and also to further investigating the quality of samples. The methods we propose to use include PEA (with a new panel of intracellular proteins) for protein analysis, and gene expression analysis by RNA seq. 18

19 Project groups Proteomics project: Emma Rennel, Ida Grundberg (Olink), Masood Kamali Moghaddam, Rachel Nong and Spyros Darmanis (IGP, Uppsala University), Gunnel Tybring and Mark Divers (KI, BBMRI.se WP6) and Joakim Galli (BBMRI.se WP4). Metabolomics project: Thomas Moritz and Linus Malm (SLU, Umeå, BBMRI.se WP4), Gunnel Tybring and Mark Divers (BBMRI.se WP6) and Joakim Galli. Tissue fixation project: Joakim Galli, Elin Lundin, Ola Söderberg and Mats Nilsson (IGP, Uppsala University), Uwe Oelmuller, Karl-Friedrich Becker and Sibylle Gündisch (Qiagen and SPIDIA project, Germany). Research on cytology biobank samples: Joakim Dillner and Nasrin Persqvist (KI and WP3), Joakim Galli and researchers from SciLifeLab analysis platforms. Biobanking Analysis Resource Catalogue (BARCdb) Background Within BBMRI.se, WP4 has developed the Biobanking Analysis Resource Catalogue (BARCdb, a freely available web resource, listing expertise and molecular resource capabilities of research centres and biotechnology companies. The database is designed for researchers who require information on how to make best use of valuable biospecimens from biobanks and other sample collections, focusing on the choice of analytical techniques and the demands they make on the type of samples, pre-analytical sample preparation and amounts needed. Service provider information is presented in the form of resource cards which summarise the services available and the contact details for potential users. Currently there are about 150 cards online, mostly relating to Swedish providers, but the coverage is being extended to the whole of Europe. The information is regularly updated by the providers who have agreed to make their resources available. The value of the catalogue lies in providing the information about where services can be obtained in a simple and readily accessible form, information that is not always easy to find. BARCdb can help to match resource providers with potential users, stimulating transnational collaborations, and ensuring compatibility of results from different labs. It can promote a more optimal use of European resources in general, both with respect to standard and more experimental technologies, as well as for valuable biobank samples. The catalogue also provides: up-to-date information on reagents, such as antibodies, useful for analyses of biobank samples up-to-date information on omics technologies, service providers, and relevant organisations Search functions to identify suitable molecular tools, reagent collections, and service providers Step-by-step guide for setting up omics analyses by offering suggestions about which techniques are best suited for each specific research project (to be implemented) 19

20 A news section (to be implemented) with new developments of molecular techniques and relevant courses and conferences Mission (i) To optimise interactions between providers of analytic resources and researchers that use biobank samples. (ii) To provide up-to-date information about molecular technologies, reagents, commercial products, service facilities and contacts to technical experts for users of biobank services. (iii) To assist with advice about how researchers can best make use of valuable samples, from preanalytical handling and sample preparation to the choice of analysis techniques and their providers, and what the requirements for the techniques are. (iv) To offer advice in the planning for sample collections to meet analytical possibilities and requirements of emerging technologies Goals and Deliverables The BARCdb database will be further developed in a number of ways, including: Continuous expansion by inclusion of additional company and academic resources providing technologies and products for analysis of biobank samples in Sweden. Expansion to include more European resources. Collaboration has been initiated with the corresponding BBMRI work packages in other European countries. An improved design of the database to simplify webpage navigation. A news section on the front page, including short articles describing technology and instrument developments that are provided by the various platforms, facilities and companies. The section will also include information on relevant courses and conferences. Technology watch, summarising new resources for analysis. Providing benchmarking reports that compare technologies in the different omic field, which will serve as a guide for researchers to find the optimal tools for their research. A manuscript describing BARCdb has been submitted for publication to the annual database issue of the journal Nucleic Acids Research. Timeplan BARCdb is being continuously updated and new resource providers are joining. The new BARCdb design and the news section will be implemented during Q Project group BARCdb is mainly being developed at the department of Immunology, Genetics and Pathology, Uppsala University, by Joakim Galli and Johan Oelrich. Support is provided by Eva Ortega (Lund University) Prof. Ulf Landegren, Dr. Mike Taussig (Cambridge, UK) and Prof. Frank Skorpen (Trondheim, Norway). Training and dissemination 20

21 Background and mission Guidance and advice WP4 provides expert advice and guidance on a national level to researchers of relevant technologies, covering all omics fields, for analysis of biobank samples, especially those technologies provided at the respective facilities where WP4 coworkers are employed. Furthermore, WP4 will provide guidance for pre-analytical steps, such as sample collection and storage, as required for the intended analyses. Conferences/Courses We propose to organise regular technology workshops, courses or conferences. In October 2013 the first BBMRI.se course for PhD students in biobanking was organized. The course was organised as a collaboration between WP4 and WP6 (Gunnel Tybring), with the aim to give participants insights into the process of biobanking from ethical and legal aspects, collection, preanalytics, and modern technologies for analysis of samples. Goals and Deliverables Guidance to researchers Guidance at a national level is continuously being offered by the WP4 coworkers in Lund, Stockholm, Uppsala and Umeå, to researchers using biobank samples or in the process of setting up new samples collections, providing advice on advanced molecular technologies for analysis of biobank samples. Guidance on preanalytical handling of samples We are developing an online platform that will be part of the BBMRI.se web page, regarding pre-analytical variables in biobanking. This platform will summarise the current literature and provide guidelines on pre-analytical handling (sample handling, storage, processing, etc) with respect to the various analysis technologies in use. The platform will provide up-to-date information on all aspects of pre-analytics that helps researchers to avoid unwanted errors due to pre-analytical handling. Course in biobanking and conference on advanced molecular technologies We are planning a second biobank course for PhD students in collaboration between WP6 and WP4. The course will be held at Karolinska institutet. Furthermore, we are planning to organize a conference on advanced molecular technologies for analysis of biobank samples. The conference is to be held at Uppsala university. Timeplan The biobank course for PhD students and also the conference on advanced molecular technologies are planned for Q3-Q A first version of the online platform for preanalytical variables will be available in Q at the BBMRI.se homepage. 21

22 Project groups The course in biobanking and sample analysis are organized by Gunnel Tybring, Cecilia Björkdahl (Karolinska institutet, WP6) and Joakim Galli. Guidance on sample analysis: Eva Ortega-Paino and Ulrika Andreasson (CREATE Health, Lund, BBMRI.se WP4), Jacob Odeberg, (SciLifeLab, WP4) Linus Malm (SLU, Umeå, BBMRI.se WP4) and Joakim Galli, (IGP, Uppsala, BBMRI.se WP4). Platform for preanalytical handling: Eva Ortega-Paino, Gunnel Tybring, Joyce Carlsson (Lunds University) and Joakim Galli. Technology networks and coordination with other initiatives Background In order to promote biobank research and link analysis tools to biobank resources for basic and clinical research, collaborations have been established with groups and centres providing access to analytical resources within Sweden, including SciLifeLab in Uppsala and Stockholm, Umeå Metabolomics facility, and CREATE Health Translational Cancer Centre in Lund. We are currently expanding the network to include the corresponding activities in other Nordic countries, initially through regular meetings. We continuously monitor emerging analytical techniques and identify gaps in analytical services for biobank users, which we strive to fill in collaboration with other initiatives. Mission We have participated in the collection and use of valuable biobank material over many years. Our aim is to maximise the availability of methods and adapted them to serve emerging analysis requirements and opportunities. Goals and Deliverables Coordination The work described herein will be coordinated with the other workstreams in BBMRI.se, and with other national projects, such as BILS (Bioinformatics Infrastructure for Life Sciences) and the SciLifeLab. The project is also coordinated with EU Research Infrastructure projects including BBMRI.ERIC, those in clinical translational medicine namely EATRIS (European Infrastructure for Translational Medicine), and ECRIN (European Clinical Research Infrastructure Network), and large-scale data handling (ELIXIR). This work is continuously ongoing and it is not possible to set up a detailed overall time plan. The Molecular Methods (MolMeth) database Background This is a publicly accessible database for laboratory protocols, including standardised methods and data storage recommendations, for analysis of DNA, RNA, proteins and metabolites, applicable to biobank samples. It is a structured database created by BBMRI.se WP4 partners 22

23 with the aim of providing best practice-based protocols for molecular analyses of different types of samples. Even though MolMeth is functional and open to the public, it remains under continuous development. Relevant items provided include: Standardised protocols for biobank sample processing Standardised protocols for molecular analysis of samples SOPs for sample handling Versioning and history system for protocols Opportunity for collaboration and sharing of methods between labs through password protected areas Mission (i) (ii) To make protocols and SOPs for collection and use of biobank material available in an open access database To provide a digital infrastructure for harmonisation of biobanking practices. Goals and Deliverables To make a greater number of high quality laboratory protocols available to researchers. To create groups dedicated to specific research topics and knowledge sharing. Collaboration with provider companies to make it easier for researchers to compare commercial protocols Improved search functions such as taxonomy searching and similar protocols. Connections to biomolecular resources such as BARCdb, Antibodypedia, IntAct and others Connections to commercial vendors and scientific publications. Create stronger connections to minimum information, ISO- and GxP-standards Establish collaborations with biobanks to provide comprehensive coverage of protocols for all aspects the Biobank process. Project group The main development of MolMeth is carried out at the SLU global bioinformatics centre by Tomas Klingström and Erik Bongcam-Rudloff. Support is also provided by Joakim Galli (BARCdb extensions and Johan Oelrich (BARCdb/search engine development) at Department of Immunology, Genetics and Pathology, Uppsala University and Larisa Soldatova (Ontology development) at Brunel University, UK. 23

24 BBMRI.se Service Center for Southern Sweden The BBMRI.se Service Center for Southern Sweden will provide a real-life pilot implementation test of the concept of an integrated, regional BBMRI.se Service Center that will provide assistance to researchers wishing to use biobanks - in all the different areas where the support is required. During the first 5 years of BBMRI.se, support to the biobank-based research infrastructure in Southern Sweden was given through at least three different work packages, with exploratory discussions on provision of support with 2 additional work packages. Although this resulted in a fragmentation of services, the regionally employed personell is now firmly engaged in the national networks of BBMRI.se in all the different areas of expertise (former work packages ) and it should be possible to provide more effective and concerted services in an interdisciplinary, regional BBMRI.se Service Center with close and effective collaborations to other service providers, both in the region (notable the healthcare provider Region Skåne), nationally and internationally.the BBMRI.se personell currently employed at Lund University works either at the Medical Faculty (in former WP2, supervisor Peter Nilsson) or at the Technical, Natural Science Faculty (in former WP4, supervisor Carl Borrebaeck). In addition, support with sample handling and provision of equipment for this has been provided by former WP6 (now National Service Center for Sample Management). The work during 2015 will constitute a piloting on how regional BBMRI.se Service Centers could operate. The following goals will constitute the work plan for 2015: A. Sustainability -Provide a clear operational plan for the Service Center that will include the costing and financing (including users fees) for the services provided. -Develop a standard list of services, starting with services that are essentially already operational namely: Access Services; Cohort Enrichment Services; Study Coordination Services; Services with advice on appropriate Analysis Technologies and Reagents; Services with advice on IT technologies for biobanking and biobank-based research; Services with advice on Innovation and Services with advice on Sample Management. These services will all be developed and continuously improved in collaboration with both regional service providers (in particual the regional healthcare provider Region Skåne), with the network of BBMRI.se services provided in other parts of Sweden and in collaboration with BBMRI-ERIC service providers in other parts of Europe. B. Communication and Education Collaborate with the regional healthcare provider Region Skåne as well as with other BBMRI.se Services and Service Centers regarding providing information about BBMRI.se, engage in customer dialogue and provide education in biobanking and biobanks-based research. 24

25 BBMRI.se Access and Cohort Enrichment Service Center(s) The overall aim of the Acess and Cohort Enrichment Centers (ACE centers) is to promote and initiate various collaborative projects to establish new infrastructures in different disease areas and to ensure that existing and planned BBMRI platforms are utilized in an optimal way. The ACE centers are also involved in the further development of biobank systems for quality assurance, including corresponding legal matters and a national directory for omic-data combined with a system for reuse of omic-data according to the demands of the research council. The practical work is adapted to the needs and the resources available at each center site. The ACE centers are involved in building up the new combined infrastructures by facilitating links with registries and working on standardizations between biobanks. The newly formed combined biobank are examples of infrastructures permitting world leading biobank research and thereby fulfilling a second demand from the Swedish research council on BBMRI.se. The newly formed infrastructures, which can take years to build up, are established in a way that permits reuse for testing of various forms of follow up studies or for completely new hypotheses. To further develop a quality assurance system to be applied on biobank projects and their interactions with registries It is important that biobanks have similar quality systems. Currently, there are several international efforts to standardize quality systems for biobanks. These must be evaluated and practical administrative applications adjusted to Swedish circumstances must be proposed and communicated within BBMRI.se. The mission is to facilitate the coordination of national studies by improving cooperation with biobanks and registries and to combine them in the best possible way. Today many scientists are facing practical problems in getting data from quality registries and sometimes from biobanks, in an efficient way. Our mission is to facilitate this process. Discussions on how to improve the use of registries and other clinical data are ongoing at the regional level with both administrative leaders and politicians. One goal is to raise the appreciation of medical research within the hospitals in order to position research activities at the same priority level as other health care activities. What is research today is hospital care tomorrow. Regional discussions are expected to reach this aim. Pilot discussions held in northern Sweden have so far been very promising. Action plan, goals and deliverables The overall aim is to establish a cost effective system for biobank research with the following components: To optimize the cooperation with the county councils. This cooperation is crucial for success when working with access to biobank samples from the healthcare system as well as data from quality registries. Three agreements in Northern Sweden have solved all major problems in that area. 25

26 Discussions for improvements in the cooperation with counties are ongoing in Stockholm and region Skåne. In some areas the cooperation is already working efficiently, e.g. Uppsala, Linköping and Göteborg. To further develop the QA systems, with regards to the practical handling and legal aspects of the research materials. The legal rights and positions of scientists, supported by the Swedish Research Council, are important in order to achieve the goal of becoming a world-leading nation in biobank infrastructure. To continuously promote discussions with the National Data Inspection Board to find practical solutions to optimize research. The challenge is now to work together with NCI for posting omic data on a secure web site at NCI. So far with little success. The strategy at the moment is to convince NCI to sign the EU document needed for this cooperation. Legal advice has also been asked from other EU countries, e.g. Imperial College in London. So far no answers. Another solution has been to move interpretation of data to Europe, with some success. During 2015 all test using metabolomic and other biomarker methods concerning sample quality should be published or made available somehow within the BBMRI.se family. Practical guidelines for the use of registry data and when and how to apply for ethical approval. A new system for pre-identification of cases has been launched in Umeå and will be followed up during Monitor and follow up deviation reports from the scientific process within the participating biobanks. During 2014 reports on sample quality and legal matters has been distributed among the participating biobanks. In 2015 an improvement of sample quality is expected in some projects. Changes in sample handling will occur within the LifeGene project and possible within the EpiHealth project. The purpose is to improve sample quality when possible, otherwise clearly describe sample quality at each sampling time. The target is that changes will occur during 2015 with implementation of improvements of the collection system in some studies. To continue the discussions with Statistics Sweden to insure the use of personal numbers on the regional levels at universities and university hospitals. Practical guidelines for how to work according to new legislature as well as the rules of Statistics Sweden and the National Data Inspection Board are discussed directly with the two organizations, at seminars and by correspondence between scientists. During 2015 the practical implementation of a new system is expected to occur with direct handling of SCB personal numbers in at least one university in projects on disease prediction. To stabilize the position of the research coordinators at the different universities participating in BBMRI.se. The national organisation is now in place and fully operative with one exception, Örebro, which is expected to join in A stabile organisation is needed for keeping quality on a high level and for interaction purposes within the country. Supportive actions have also occurred within the organisation to give active support between partners. Omics studies within BBMRI.se Large amounts of GWAS (genome-wide association study), metabolomic studies and other omics studies are performed on various biobank samples in Sweden. It is possible that the objective of a Swedish reference population could be reached simply by coordinating already ongoing work. That process is almost finalized in one area. It has become evident that due to the rapid development of genetic analyses, GWAS materials are quickly getting old. In order to increase power and to limit false positive findings resulting from population differences optimal reference populations should be selected for each study. Several studies have been launched reusing 26

27 GWAS data in the Umeå biobank with a participation of different national and international groups. More studies are in pipeline involving also other universities. Action plan, goals and deliverables Several omic studies are initiated and some are finalized. The process of organizing and reusing the results has started. A national catalogue for omics data (genomics, transcriptomics, proteomics, metabolomics, lipidomics) is being discussed and implemented in cooperation with other parts of BBMRI.se in order to simplify for scientists in Sweden to collaborate on large scale omics projects. The results of the pilots in Umeå concerning reuse of GWAS data have been successful and a new organisation has been formed. GWAS results have been reused in several projects by scientist with national and international affiliations. Supplementary organisational structures like the MethaHealth infrastructure are expected also to be used for this purpose. Existing GWAS data can be kept in the BBMRI.se sample collection register coordinated by Loreana Norlin in Stockholm. A process of quality control using metabolomics, transcriptomics and possibly proteomics and/or specific biomarkers applied on different biobank samples has been initiated. This infrastructure will be further developed during 2015 and the publications presented. To interact with one national organization with support from the Research Council, managed from Linköping, Bioinformatics Infrastructure for Life Sciences (BILS) concerning reutilization of omic data. An interactive process is ongoing in Umeå. This process is partly successful (one new individual employed within the area of using genealogies), partly failed while no candidate was found for a BILS position in bioinformatics stationed in Umeå. Coordination of biobank infrastructures in Sweden to establish new world leading infrastructures in specific areas When BBMRI.se was planned the intention was that research coordinators should be employed at all the medical faculties in Sweden to promote strong national cohort collaboration. A large number of new infrastructures have been established during this process. The mission was to promote and initiate national infrastructures which have the potential to reach a world leading position regarding a number of disease areas which were reported in the introduction according to the demands of the Swedish research council. By definition the new infrastructures must be established in such a way that it can be reused for testing other hypothesis than originally planned. Action plan, goals and deliverables The new infrastructures developed with support from the ACE centers must be clearly defined and evaluated during A large number of infrastructures have been reported to the BBMRI.se board and the Swedish research council. Those defined as word leading according to the demands of the research council and according to predefined criteria must be motivated to be associated with that comment. 27

28 New dimensions in combining genealogies with classical biobank research are expected and several projects have been established on the infrastructure. Of specific importance are the projects of disease prediction. Deliveries must be given within this area while the area was emphasized in the funded BBMRFI.se application. The first infrastructures for familiar cancer are progressing well as well as a project for imputation of genetic information. A number of epigenetically oriented projects are progressing. A new system for predicting disease using the combination of biomarkers, omic data and genealogies will be launched in A Swedish Cohort Consortium will be organized. The BBMRI coordinators are involved in supporting a very large number of infrastructures already reported to VR. This process will continue during 2015 and more studies will be added. During 2015 those infrastructures which meet the criteria s of a participation in a national Swedish Cohort Consortium will be identified. The ACE centre s steering group has agreed on the general principles to be used to select infrastructures into the consortium, but several questions are yet to be answered concerning planning, funding and organisation. To further stimulate the development of new national and local disease registers that are going to be used in biobank studies and to facilitate the collaboration with already existing disease registers. In many areas the national registries are working nicely, in some areas there has been less improvements. One way of solving current problems is to promote existing or future registry platforms operating at the Swedish universities and university hospitals. A successful cooperation with the disease registries is crucial for the long term success of BBMRI.se. Obstacles of biobank research will be further defined and if possible solved within the framework of the Fort Knox project where different experiences in the past and in the future will be documented. Practical cases have been presented and a process of implementation of more efficient processes is expected. Within BBMRI LPC a sufficient amount of information and samples will be available also for prospective studies on rare diseases. Opportunities for large scale funding (e.g. in the context of H2020) will be identified both for the newly formed infrastructures and for specific projects attached to the infrastructures. It is important that applications related to the BBMRI.se infrastructures are identified and used for the financial structure of the future BBMRI.se. A system for environmental monitoring will be developed further. The National Human Environment Specimen Bank is an environmental health network: Swedish prospective biobanks have unique features for studies of effects of environmental pollutants. A network of environmental health researchers will be formed, probably in connection with the toxicological resource Swetox and possibly also with a network for environmental human sampling formed by the Swedish Food Administration. It will invite environmental health researchers from all universities participating in BBMRI.se or Swetox. A time-trend sample set for contaminants, as well as other biomarkers, will be established within the NSHDS cohort, as well as a repeated sample set for assessment of within and between-individual variation and calculation of attenuation of dose-response curves. A detailed action plan is written for the national immunity and microbial biobank. The implementation of the biobank part of the project is expected to take place during the influence epidemics expected in Sweden 2015/2016. During the first part of 2015 the national biobanks will be selected for this purpose and test performed on how fast sample retrieval can be performed in various biobanks. Based on this pilot the test study will be organized during the influenza epidemic. Thus an important component of such a contingency would be the rational use of samples from existing biobanks to enable fast prediction of population susceptibility to infection and the mapping of the 28

29 spread of infections. The large amount of available information may also clarify the more complex, yet unknown connections between the genetic components that predispose to infection or that are linked to the severity of infections. There are also very large microbial sample collections in biobanks in universities and hospitals, and they can, if they are made available nationally, become unique resources to develop strategies to control one of today's fastest growing medical problems, antibiotic resistance. Analysis of the microbial biobanks would thus give us essential information on changes of antibiotic resistance. A national coordination that allows the microbial biobanks to be linked to the human biobanks can provide invaluable information about the factors that predispose to the occurrence and spread of antibiotic-resistant bacteria. A detailed research program describing the project is now available. Dietary trends in NSHDS Umeå. Within NSHDS, dietary data has been collected with a food frequency questionnaire (FFQ) since This gives us the opportunity to follow trends in dietary intake in the northern Swedish population. As an example, consumption of fat was found to decrease evidently in the county of Västerbotten in the beginning of the collections, but started to increase again, on expense of carbohydrates, around 2004, and are now at even higher levels compared to in the mid 80 s (Figure). The interest in the impact of diet in the Swedish population is great but also confused. Coordination of cohorts is needed to get more solid results on a national level. Different organizations in the society and medical journalist are demanding such an action. The dietary trend organization is organized within the environmental biobank described before. Pilot studies have been initiated to collect clinical data at the centres. This process will continue during One component is pilot studies combining various forms of biobanks with imaging techniques in Alzheimer s disease. The use of new biomarkers for biobank research and disease prediction will be promoted. In Uppsala both fatty acids for an estimation of dairy fat intake (C15, C17) has been developed and a new method for estimating amount and quality of whole grain, the alkylresorcinols. Both methods have been accepted internationally. Using metabolomics and proteomics the centers in Uppsala and Umeå are expected to develop new biomarkers for diet, metabolism and disease prediction. An innovative process is ongoing. The NorthPop child cohort is now cleared from the ethical committee and the operational phase will start soon. Experiences from the LifeGene project and the Mother 29

30 and Child project in Norway are used. Pilots have been performed. The it-system of NorthPop will be the same as that used by LifeGene to promote national coordination. Extended cooperation with national and international biobank networks on public health issues with the identification of success stories. The cooperation within international biobank networks in pooling of samples and data has been ongoing since several decades, in order to increase statistical power and to study international trends. This collaboration is expected to further expand in the future with the objective of addressing common important public health issues. The mission is to identify the national and international success stories where biobanks/epidemiology has been used for major discoveries of significant public health impact in Sweden and internationally. Action plan, goals and deliverables To evaluate how effective the cooperation are in different international networks in relation to scientific outcome and funding. To identify several national projects with a specific public health message. A detailed plan for describing some success stories is available. It will be implemented in To communicate the process behind the public health discoveries to the public via media with the purpose of motivating biobank/epidemiological research and to promote further funding of future biobank research. To identify new areas for specific public health interventions. To give support to the BBMRI.se application for funding from

31 MANAGEMENT To increase the flexibility and coherence of BBMRI.se, the management sector will be significantly strengthened by i) the direct fusion of several former work packages to become Central Services directly reporting to management, in particular the work on information technology, support for health care biobanking and studies on sustainability and economy of BBMRI.se. ii) prioritization of the work on communication, for a strengthening and formalization of information and dialogue channels to ensure that all achievements and intentions of BBMRI.se are well recognized and that our organization is characterized by transparency and responsiveness to feedback. Iii) launch of Strategic Supportive Actions that are intended to ensure that BBMRI.se will be a flexible organization that can design tasks to meet urgent unmet needs and respond to international and national opportunities when they arise and iv) In areas with an clearly discernible unmet need, but where the optimal way forward is not obvious, engage in investigations and discussions with other stakeholders and customers in order to find sustainable ways to meet the needs. Activities of the BBMRI.se Communication Plan BBMRI.se communication activities are aimed at: - Increasing the awareness for the tools, resources and guidanguidelines developed within BBMRI.se, - Illustrating how successful biobank-based research is dependent on efficient access to a variety of resources (not only to the samples), such as registers, large-scale analysis techniques and bioethics research and advisory. - - highlighting the importance of successful biobank based research for advances in medical diagnosis, treatment efficiency, health and welfare, as well as Sweden's competitiveness in a wider perspective, - - analyzing and comment on the events of importance for biobank research and BBMRI.se based on an ethical, legal and social perspective - - creating solidarity within the organization - - influencing the development of biobank-based research in an international perspective. The above objectives can be achieved through long-term work and communication through multiple channels. In 2015, we will systematically address the challenges of adequate communication using a formalized Communication Plan that will include, for example: -the newsletter biobank SWEDEN, which is sent out to more than 2500 people. -the biobank webinars highlighting the research in the area and creating a sense of community to 31

32 the field. -strong presence in social media (blog, twitter, LinkedIn). -press release policy -joint retreats for all co-workers BBMRI.se Central Services The BBMRI.se central services are highly prioritized services that provide service to customers all over the country. Because of high priority, rapidly changing fields requiring flexibility and a rather small critical mass of co-workers, these services will report directly to the BBMRI.se administration. During 2015, three such Central Services will be offered: -BBMRI.se Services for Support to Healthcare-based Biobanking -BBMRI.se Information and Technology Services -BBMRI.se Fundraising and Financing BBMRI.se Services for Support to Healthcare-based Biobanking The goal is to develop and implement a long-term strategy for systematic, standardised and nationwide biobanking in healthcare, finding new ways for optimizing build-up, usefulness and accessibility of clinical biobanks. In major clinical areas such as clinical chemistry/pharmacology, clinical pathology clinical cytology and clinical microbiology, we will develop strategies for nationally coordinated enrolment, sample management, storage and exploitation that will optimally serve the needs of these different clinical disciplines. Major rationales behind this strategy are: -The major Healthcare-based biobanking that has both greatly benefited the development of healthcare itself, the diagnostics of the patients and has become a widely used research infrastructure are the systematic biobanking such as the clinical pathology archives. By analogy, it is likely that the largest gain for supporting both healthcare and for developing a sustainable and widely reused research infrastructure is to support systematic and sustainable biobanking linked to different clinical disciplines. BBMRI.se has so far launch efforts to support systematic biobanking in clinical cytology and in clinical microbiology. These will be strongly pursued during 2015 while preparations for a possible launch of a third area targeted for BBMRI.se support will be pursued. -The clinical development work for strengthening and modernizing the systematic clinical biobanks tends to not be nationally coordinated, which may result in duplication of work, higher costs, impaired standardisation and slow progress. -In the BBMRI.se concept, the development is performed jointly in a national network and BBMRI.se is financing personell to administrate the nationally coordinated development. -Joint development of technical & logistical solutions, QA-systems, IT-systems, standardisation & Standard Operating Procedures, minizing costs incurred by duplication of work and non- 32

33 standardised solutions. -National purchasing performed by BBMRI.se will reduce costs because of large volumes and simplified development work for the supplier (many parts of the country order exactly the same solutions). The national purchasing will also automatically result in a national standardisation of the procedures and formats for how the clinical biobanking is performed in different parts of the country. -Nationally standardised biobanking will enable valid use of materials from many different regional biobanks for nationally and internationally competitive research (Local formats can only be used for local research). Clinical cytology BBMRI.se has developed the liquid-based clinical cytology biobanking method in 12 counties (Stockholm, Gothenburg, Örebro and Umeå amongst others) around the country. The number of stored cell samples in the spring of 2014 was >300,000 samples. The sample quality is checked twice a year by random sampling. Withdrawal and use of samples from the cytology biobanks are handled according to the same national ethical and legal requirements at the respective nodes as are already in place. During 2015 we will further expand the BBMRI.se standardised automation solution for clinical cytology that is now serving a majority of Sweden with state-of-the-art, nationally standardised biobanking. Clinical microbiology Microbiological Laboratories in Sweden store a large number of samples to enable later diagnostics. BBMRI.se has developed and made a national purchasing for a standardized automation solution for clinical microbiology. We will work on making these available for research with focus on a well-defined set: blood samples from pregnant women. BBMRI.se runs a project to standardize the process of saving and offers storage space for samples and expertise in database management. The BBMRI.se national repository for samples taken during Maternity Care will enter the routine activity phase as a national resource for research on healthy childbearing. The samples are a unique resource for epidemiologic research into health of women and child and for research into identification and qualification of diagnostic markers. To date some 65,000 serum samples are already stored in the BBMRI.se national repository for maternity care samples. The likely annual growth is about 30,000 serum samples. One of the scopes during 2015 will be to increase the use of these samples by making them accessible in a searchable database ( Maternity care samples database ) including possibilities for matching with registries and identifying samples for study. We will also start a project to develop harmonization and dissemination of so-called "best practice". Furthermore, the BBMRI.se national repository will also be providing service to nationwide or international biobanking projects, with the Umeå-based Swedish node of the healthy aging research infrastructure SHARE-ERIC as a prime example. 33

34 During 2015, we will also investigate possible avenues that could be pursued in order to develop a national platform for biobanking in clinical pathology. Information Technology Services Enhancing accessibility by enhancing visibility: The BBMRI.se Sample Collection Register ( contains descriptive data about sample collections and related data in Sweden. The purpose is to help researchers to navigate the landscape of Swedish biobank studies and to provide a tool for finding collaborative partners and biobank samples for research. The Sample Collection Register is based on the Minimum Dataset, MIABIS. During 2015 BBMRI.se will continue promoting, enhancing and extending the register with sample collection meta-data. This work is also of high importance for building of the new BBMRI.eu catalogue in which BBMRI.se will have an active role during All new sample collections in the BBMRI.se National Service Center for Sample Management must be able to provide meta-data about the sample collections to the BBMRI.se Sample collection register. Business Intelligence solution development for researchers: turning data into knowledge DI-LPC (myreserach.se) This work has received separate funding (until 2016) from the Swedish Research Council, but will be performed in close collaboration with BBMRI.se and will be reporting to the board of BBMRI.se. Several very large-scale Swedish cohorts that use BBMRI.se services for sample collection are using the same IT platform for collecting the baseline data, further enhancing their comparability. The purpose of the project is to extend the existing IT service platform, incorporating key Business Intelligence (BI) functionality in accordance with customer needs allowing customers to view, manage and share their collected data. This is a requirement by most potential customer cohorts if they are to adopt the services in their own research projects. The BI services will increase the customer base and attain long-term economic sustainability for the services. On the EU level, we will in particular be supporting the development of jointly developed Open Source IT tools in this area, for example the MAELSTROM system. LIMS & International Cataloguing BBMRI.se has entered an agreement with the WHO/IARC (International Agency for Research on Cancer) that has launched an international Biobank & Cohort Network (BCNet; primarily focussed on helping with the development of biobanking services for Low and Middle Income Countries (LMICs). BBMRI.se will be working towards an international biobanking catalogue on the sample level that can be used for the entire BCNet. Also, BBMRI.se will through BCNet support biobanks in LMICs to increase the level of awareness, education, and biobanking infrastructure and to address the underavailability of highquality biospecimens for cancer research in LMIC countries. 34

35 Standards: MIABIS and OMIABIS One of the major challenges in biobank research is to close the research cycle in a way that all the data generated by one research study, can be consistently associated to the original sample and hence be reused in another studies. MIABIS represents the minimum information required to initiate collaborations between biobanks and to enable the exchange of biological samples and data. The aim is to facilitate the reuse of bio-resources and associated data by harmonizing biobanking and biomedical research. BBMRI.se is leading the working group established in November 2013 with 20 country experts from five BBMRI-ERIC countries to work on the governance and shaping of MIABIS 2.0. The goal is to have MIABIS accepted as a de facto biobank standard by all BBMRI-ERIC member states by BBMRI.se will continue hosting the public BBMRI-Wiki site where updates to MIABIS are published and a data model is provided for free download. We will also collaborate with ontologists from University of Arkansas for medical sciences and University of Pennsylvania to provide an ontology for MIABIS 2.0 during Contributing to and learning from EU-projects The BBMRI.se co-workers that are working with the Information Technology Services are actively contributing to several international projects and networks. Through this we make sure that the work done in Sweden is harmonised with other similar ongoing work in Europe. We are involved in the following established EU networks and projects: EU Project BiobankCloud Description PaaS for high-thoughput biomedical data storage, analysis and shring (WP1, WP8) BioMedBridges Twelve biomedical research infrastructures develop the shared e- infrastructure the technical bridges to allow data integration in the biological, medical, translational and clinical domains and thus strengthen biomedical resources in Europe. KI-WP3, WP8, WP10 RD-Connect BCNet EUDAT An integrated platform connecting databases, registries, biobanks and clinical bioinformatics for rare disease researc (WP3) Global biobank network for IARC. BBMRI.se develops international biobank catalogue at the sample level for BCNet European Data Infrastructure that integrates HPC and storage facilities to provide research from different domains with informatics infrastructure for data storage, processing and sharing. BBMRI.se contribute to create the BBMRI-ERIC community Sustainability, Financing, Fundraising & Strategy Formerly run as a separate work package, this activity will now be run as a part of the overall management and administration of BBMRI.se. During 2015, the major goals will be to: 35

36 i) develop a professional Business Plan for BBMRI.se, where the advantages of BBMRI.se are clearly outlined for all stakeholders and financing agencies with regards to the expected returns on investment. ii) Develop a strategy for launch of a Swedish Biological Expert Center in close collaboration with the development of Biological Expert Centers in other EU countries within BBMRI- ERIC. Expert Centers as Novel Solution to Address Ethical and Legal Restrictions There are several examples of outstanding research collaborations between public institutions and industry. In the context of such research collaborations also access to biological samples medical data and scientific expertise is granted. However industrial partners often need access to samples for pilot studies that are required for prioritizing future research programmes. In such situations industry is willing to pay for accessing samples and medical data since research collaborations are not feasible and it is unlikely that scientific publications emerge. Such financial compensations are not accepted by the public (patients, sample donors, patient organizations etc.) or medical professionals not directly benefiting (Nature 461: ). Commercialization of human biological sample and medical data is prohibited in the European Convention ETS164 and in national legislation of most Member States. Although financial compensation on a cost-recovery basis is allowed it is generally not accepted by the public. On the other hand high quality samples can t be provided to the industry without any scientific incentives or compensation of the public investments into building up these resources. This situation is a source of conflict that makes the access for industry difficult or even impossible in many cases. Expert Centres that operate on a not-for profit basis could be an efficient solution for this problem. The Experts Centres could perform for the industry on fee-for-service basis the analysis of samples using latest technologies that operate at high level of standardization and quality management, and integrate scientific and medical expertise. Expert Centers as the Future Highways for Transnational Research Collaborations Several countries like China, Russia, Brazil, India have legal restrictions on export of biological samples that make transnational research collaboration difficult. The establishment of partner Expert Centres in Europe and non-european countries that operate under same standards and quality management schemes could generate highways for future transnational research collaborations since samples will be analysed in the country of origin and only research data are shared (Figure 1). 36

37 Figure 1: Expert centres as new highways for transnational research collaborations Strategic Supportive Actions The Strategic Supportive Actions are intended to ensure that BBMRI.se will be a flexible organization that can design tasks to meet urgent unmet needs and respond to international and national opportunities when they arise. Different Strategic Supportive Action may have different lifespans, with some Actions being undertaken only during a rather limited time while others may become the seed of more large-scale and long-term operations. During 2015, the following Strategic Supportive Actions are envisaged: -BBMRI-ERIC Supportive Actions -BBMRI-LPC Supportive Action -National Infrastructure building projects: -NorthPop Child -SCAPIS Plus -SWECRIT -Swedish Cohort Consortium Supportive Action BBMRI-ERIC Supportive Actions BBMRI-ERIC Supportive Actions are intended to support the development of BBMRI-ERIC. Sixteen Member States, including Sweden, and one International Organisation have established BBMRI-ERIC, one of the largest health Research Infrastructure in Europe today. BBMRI-ERIC primarily aims at establishing, operating, and developing a pan-european distributed research infrastructure of biobanks and biomolecular resources. Combining the expertise of the clinicians, pathologists, bio-informaticians, and molecular biologists involved, a globally unmatched, 37