Operational plan 2015
Operational plan 2015 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 2016-2023. 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 7th 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 2015. 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 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 2013. 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 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 20141118 Joakim Dillner Acting Director, BBMRI.se 4 Contents BBMRI.SE NATIONAL SERVICE CENTER FOR SAMPLE MANAGEMENT ................................................. 8 BACKGROUND .............................................................................................................................................................. 8 OVERALL GOALS FOR 2015 ........................................................................................................................................ 8 WORKSTREAMS AND GOALS ....................................................................................................................................... 9 BBMRI.SE NATIONAL SERVICE CENTER FOR ETHICAL LEGAL AND SOCIETAL ISSUES (ELSI) IN BIOBANKING......................................................................................................................................................... 11 ETHICAL AND LEGAL GUIDANCE BASED ON SOUND RESEARCH .............................................................................. 11 CONSTRUCTION OF INTERNATIONAL STANDARD DOCUMENTS .............................................................................. 12 CONTRIBUTING TO AND LEARNING FROM INTERNATIONAL COLLABORATIONS AND CONFERENCES ................... 13 THE ETHICS BLOG .................................................................................................................................................... 15 BBMRI.SE NATIONAL SERVICE CENTER FOR ANALYSIS TECHNOLOGIES AND REAGENTS ......... 16 EXPERT CENTRES ..................................................................................................................................................... 16 INFRASTRUCTURAL RESEARCH ON PREANALYTIC VARIABLES AND SAMPLE QUALITY ......................................... 17 BIOBANKING ANALYSIS RESOURCE CATALOGUE (BARCDB) ................................................................................ 19 TECHNOLOGY NETWORKS AND COORDINATION WITH OTHER INITIATIVES ......................................................... 22 THE MOLECULAR METHODS (MOLMETH) DATABASE .......................................................................................... 22 BBMRI.SE ACCESS AND COHORT ENRICHMENT SERVICE CENTER(S)............................................... 25 TO FURTHER DEVELOP A QUALITY ASSURANCE SYSTEM TO BE APPLIED ON BIOBANK PROJECTS AND THEIR INTERACTIONS WITH REGISTRIES ........................................................................................................................... 25 OMICS STUDIES WITHIN BBMRI.SE ....................................................................................................................... 26 COORDINATION OF BIOBANK INFRASTRUCTURES IN SWEDEN TO ESTABLISH NEW WORLD LEADING INFRASTRUCTURES IN SPECIFIC AREAS ................................................................................................................... 27 EXTENDED COOPERATION WITH NATIONAL AND INTERNATIONAL BIOBANK NETWORKS ON PUBLIC HEALTH ISSUES WITH THE IDENTIFICATION OF SUCCESS STORIES....................................................................................... 30 MANAGEMENT ..................................................................................................................................................... 31 ACTIVITIES OF THE BBMRI.SE COMMUNICATION PLAN....................................................................................... 31 BBMRI.SE SERVICES FOR SUPPORT TO HEALTHCARE-BASED BIOBANKING ....................................................... 32 INFORMATION TECHNOLOGY SERVICES .................................................................................................................. 34 SUSTAINABILITY, FINANCING, FUNDRAISING & STRATEGY ................................................................................... 35 STRATEGIC SUPPORTIVE ACTIONS .......................................................................................................................... 37 APPENDIX 1........................................................................................................................................................... 42 APPENDIX 2........................................................................................................................................................... 44 APPENDIX 3........................................................................................................................................................... 45 APPENDIX 4........................................................................................................................................................... 48 APPENDIX 5........................................................................................................................................................... 53 APPENDIX 6........................................................................................................................................................... 54 APPENDIX 7........................................................................................................................................................... 56 5 6 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 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 2002. 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, 2014. During the period of 2009-2014 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 (2010 – 2014) 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 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 >160.000 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 >70.000 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 BBMRILPC, 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 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 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 2015. 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 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 2015. 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 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 BBMRIERIC 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 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 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 2015. A publication with selected blog posts will be published. 15 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 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 (http://biospecimens.cancer.gov/bestpractices/). 17 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 Q3 2014. 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 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, www.barcdb.org), 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 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 Q1 2015. 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 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-Q4 2014. A first version of the online platform for preanalytical variables will be available in Q1 2014 at the BBMRI.se homepage. 21 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 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 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 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 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 2015. 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 e-mail 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 2016. 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 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 2015. 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 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 2015. 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 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 1986. 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 2015. 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 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 2015. 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 2016. 30 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 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 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 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 (http://bbmriregister.se/) 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 2015. 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; www.iarc.fr/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 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 2015. 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 2015. 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 BioMedBridges RD-Connect BCNet EUDAT Description PaaS for high-thoughput biomedical data storage, analysis and shring (WP1, WP8) Twelve biomedical research infrastructures develop the shared einfrastructure—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 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 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 BBMRIERIC. 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: 448 2009). 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 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 Europe-wide platform for translational medical research is envisaged with the aim to develop personalized medicine and disease prevention for the benefit of European citizens. During 2015 BBMRI.se will participate in facilitating the access to biological resources, either population-based or clinical-oriented, as well as biomedical facilities and support high-quality biomolecular and medical research. BBMRI-LPC Supportive Action The BBMRI-LPC infrastructure project is funded by the European Commission under the Seventh Framework Programme (FP7), and specifically aims to facilitate transnational access to prospective cohort studies across Europe. This will be achieved through a number of activities, for instance cataloguing of existing cohort recourses and support for access through open scientific calls. Approved applications will be provided funds for access (retrieval of biosamples and data from the participating cohorts). The next scientific call organized by BBMRI-LPC will be launched in the spring of 2015. In addition to our cohort related activities discussed above, we propose that BBMRI.se launches work to ensure that as many as possible of the Swedish cohorts that are based on Open Access are included in the BBMRI-LPC scientific calls and sets aside national funds to support the related access requests. This would allow the wider BBMRI.se community of prospective cohorts to participate in BBMRI-LPC, and greatly improve the research use of Swedish biobanks. Swedish Cohort Consortium - Supportive Action Sweden, with its unique registry traditions, is a treasure island for epidemiologists. Hospitalization or death from common diseases (such as coronary heart disease or common cancers) have been picked in many epidemiological studies for decades, but our national registries carry data also on less common events. Most epidemiological studies are underpowered for the study of those events, and those diseases are therefore incessantly discriminated. However, Swedish epidemiological studies, and ultimately patients, deserve a national effort enabling the study of less common exposures or outcome events. The most appropriate diseases to study using the Swedish Cohort Consortium those that appear in middle age or later, and that are severe enough to lead to hospitalisation or death. A collaborative effort is currently (2014) carried out within BBMRI.se with a pilot study under the name MetaHealth: Risk factors for subarachnoid hemorrhage. The pilot study will be completed and evaluated during the remainder of 2014, and the applicability of the Maelstrom suite (www.maelstrom-research.org) to this infrastructure will be assessed. The vision is to build on the experiences of MetaHealth and the existing network of prospectively collected cohorts to launch a consortium of Swedish cohorts that can compete on an international scale. BBMRI.se will just be one of several infrastructures to support this initiative. Collaboration with other European Research Infrastructures 38 The fast development of efficient research infrastructures in the European Union requires a close collaboration with several European Research Infarstructures in the biomedical area, to learn from the experiences of adjacent infrastructures, to ensure that developed services are optimally exploited by neighboring infrastructures as well as to avoid duplication of work in adjacent areas. Several research infrastructures in the biomedical area are coordinated by the BioMedBridges initiative, notably the life sciences data management infrastructure ELIXIR and the bioimage data management platform Euro-Bioimaging. Apart from BBMRI, several biomedical research infrastructures have already obtained the legal status as ERIC (European Research Infrastructure Consortium), notably the clinical research infrastructure network ECRIN, the translational research infrastructure EATRIS and the first ERIC to be launched, SHARE (survey of health, ageing and retirement in Europe). BBMRI.se is already providing samle management services to SHARE. BBMRI.se and the Nordic national biobanking infrastructures have also been successful with a major joint research grant application together with the Nordic nodes of ELIXIR (www.nordic ehealth.se). During 2015, the collaborations with other research infrastructures in the biomedical area wil be additionally strengthened, both nationally, in the Nordic region, in Europe and internationally. National Infrastructure Building Projects To ensure that the various biobank facilities in Sweden are used for large, nationwide infrastructure-building projects, BBMRI.se intends to collaborate with and support large national projects that will result in systematic and nationally collected samples and data that can be made available for others. In this cooperation it is included to receive a prioritized service from BBMRI.se Service Centers and BBMRI.se-collaborating (in the future also certified) biobank facilities, while at the same time acting as a national customer that will testing that a common infrastructure for collection, storage and withdrawal of samples can actually be made to work across the entire country. During 2015 we will collaborate with a limited number of national infrastructure building projects, proposed by different regions and selected to give a good geographical spread and make sure that all parts of BBMRI.se and collaborating biobank facilities are involved, will be launched. It is also considered essential that a number of these projects will be conducted within the health care as the involvement of health care is a strategically important issue for BBMRI.se. The vision is that all support for national infrastructure building projects will require a 50% cofinancing. For 2015, the following national infrastructure building projects are planned: 39 -SCAPIS Plus. The Swedish Heart-Lung Foundation’s (“Hjärt-Lungfonden”) very ambitious national biobanking project has a smaller part with intensive longitudinal sampling, where the longitudinal samples will be comprehensively analysed with state-of-the-science Omics technologies. This will be important both to define biological quality indicators of sample quality and to define the natural variability of the human biomarker profile. Coordinated from Gothenburg, with the BBMRI.se contact person (professor Jacob Odeberg) working at the Royal Institute of Technology. -NorthPop Children. Enrollment in northern Sweden, coordinated from Umeå. Well positioned as a national resource by making available credible work to ensure that the samples are used for research across the country (described in detail in Appendix 3). -SWECRIT. Systematic biobanking of samples from patients in intensive care. Coordinated from Lund. It is likely that during 2016-2023 additional national infrastructure building projects will become relevant (e.g. SwedeHeart and SRQ). Important areas for investigations and discussions with other stakeholders and customers during 2015 We have identified 2 areas with an unmet need, but where identification of an optimal way forward is likely to require additional investigations and discussions, namely: -National network of liquid sample collection centers -National quality assurance and certification center National network of liquid sample collection centers Many liquid-based samples have been collected for specific purposes and have had limited reuse by others. There is a need to create an infrastructure that enables nationwide collection of samples in a standardised manner with documented quality and fit for several purposes, including broad ethical approval and informed consent. Several important nationwide and systematic projects, e.g. those that accompany national quality registers for specific diseases, would need to collect samples at more than health care centers throughout Sweden. Therefore, there is a need to create a national network of biobank facilities that has the ability to collect liquid based samples for nationwide projects with the same level of quality, preferably where samples can be ordered in the electronic health record. As there are several administrative structures and already formed working groups in this area, it is not immediately obvious how BBMRI.se could assist in this area. However, BBMRI.se is strongly committed to assist in making this process come true and will engage in discussions and 40 investigations on what may constitute possible ways forward. National quality assurance and certification center Whereas great advances have been made in this regard (exemplified in Appendix 1), the mode of organization of this activity, accountability and responsibility needs to be clearer. Identification of additional approaches to promote collaboration with industry As described above, BBMRI.se is making a major effort to launch a new strategy for more efficient collaboration with industry, the “Biological Expert Center”. However, this should not be the sole strategy for promoting collaboration with industry and BBMRI.se will therefore systematically investigate how the BBMRI.se Service Centers and other services provided by BBMRI.se could be designed to optimize the possibilities for collaboration with industry. 41 APPENDICES APPENDIX 1 Not om Kvalitetsarbete Med begreppet kvalitetssäkring menas i biobankssammanhang oftast ett systematiskt utvecklingsarbete som ska säkra en god kvalitet hos biobanksprover och data. Eftersom de flesta biobanker redan idag använder sig av NBR: s rekommendationer som rör just omhändertagande av biobanksprover har BBMRI.se istället fokuserat på att dels skapa juridiskt hållbara modeller för att stödja arbetet med de svenska biobankskohorterna samt dels att upprätthålla en provkvalitet som krävs för ett flertal omic analyser och för analyser av vissa biomarkörer. Arbetet omfattar bl.a. att: försöka finna bra former för långsiktigt samarbete med landstingen. Mycket framgångsrikt i Umeå där tre avtal upprättats med den ansvarige forskaren om hur huvudkohorterna skall handhas. Separata avtal har upprättats med MONICA projektet. Liknande konstruktioner kan rekommenderas för andra universitetsorter. ge stöd till att effektivt tillgängliggöra kvalitetsregister och andra register. Här äger ett ständigt arbete rum där vi i Umeå skapat en unik modell för tidiga powerkalkyler som nu genom gått en juridisk granskning. ge stöd till tillgång till biobanksprover från svenska biobanker för stora internationella studier, ex. EPIC, NCI cohort consortium, det EU-finansierade BBMRI-LPC (Large Population Cohorts). Ett mycket omfattande arbete har lagts ned på att skapa hållbara avtal med institutioner utanför EU, dvs. avtal som kan accepteras av Datainspektionen (DI). Ett flertal överläggningar har ägt rum med DI. Dessa förväntas fortsätta i olika former. F.n. pågår en process för att få NCI att acceptera EU grundläggande regelverk som DI strikt tillämpar. stödja sammanslagning med andra data, till exempel klinisk karakterisering av fall, koppling till andra kliniska material (t.ex. tumörvävnad), etc. Här har problem, kallade Fort Knox komplexet, funnits. Problemen är delvis konstruktivt hanterade men mer arbete kvarstår. En del av komplexet är de krävande villkor som sjukvården arbetar under. utveckla tillämpningar av modern molekylärepidemiologiska tekniker för olika typer av genetiska studier och andra storskaliga omics-tekniker genom att systematiskt lagra omics-uppgifter (f.n. GWAS). Dessa skall finnas allmänt tillgänglig på samma sätt som proven. Ett system har byggts upp och ett regelverk för återanvändning har testats. En ny organisatorisk stuktur kommer inom kort att kunna presenteras. Denna struktur inkl. förvaring, uttag och regelverk kan kopieras av andra biobanker. 42 bygga nya koncept för populationsbaserade flergenerationsstudier av människors hälsa, sjukdomar och levnadsvillkor och skapa infrastrukturer för att studera utvecklingen av och förebyggande av sjukdom. Praktiska test för att använda genealogier i den praktiska patientrådgivningen förbereds f.n. via intensiva diskussioner mellan berörda forskargrupper. Diskussioner förs med SCB om regelverken som skall göra detta möjligt. Formellt måste det finnas en forskningskoppling för att SCB skall godkänna att vissa uppgifter används. skapa de legala förutsättningarna för den Nationella Immunitetsbiobanken som kräver snabb tillgång till prover. Processen har påbörjats via en myndighetsförankring (FOI, Folkhälsomyndigheten), nästa steg är troligen avtal med berörda landsting. utvärdera på vilket sätt som provers kvalitet upprätthålls, bl.a. genom att jämföra egna och andras analysresultat. Detta kan i förlängningen leda till nya rekommendationer om ex. vikten av att upprätthålla fryskedja m.m. Ett omfattande arbete har lagts ner på detta. Komplexet berör både önskemålet om snabb nedfrysning (väldokumenterat) och behov av fasteprover för många former av analyser för att minimera ex. påverkan av mikrobiotan i tarmen och kosten vid metabolomicsstudier. Ett viktigt kvalitetsarbete har också varit att försöka klarlägga i vilken utsträckning som överenskommelser inom BBMRI följs samt utreda forskarens juridiska roll bl.a. i dialog med VR. VR har i detta sammanhang levererat ett viktigt ställningstagande om forskaren som part i VR finansierade projekt. 43 APPENDIX 2 NorthPop, rapport till BBMRI.se, att. Joakim Dillner 2014-09-22 Northpop möjliggör forskning där expositionsdata och biologiska prover från flera generationer utnyttjas. Vi har en täckning av blodprover från > 80% av befolkningen i åldersgruppen 45 - 85 år i Västerbotten. Du har tidigare fått en rapport om vad som skett av Elisabeth Engberg. Du får nu även en publikation som beskriver Viking delen. Ett mycket intensivt arbete pågår just nu och Umeå universitet lägger ner en mycket stor motfinansiering till BBMRI.se. Den bifogade tabellen visar vad som skett de sista åren. Den har tagits fram efter ett möte med Marianne Sommarin, ansvarig för forskning vid Umeå universitet, veckan efter midsommar i år. Umeå universitet har gjort mycket stora infrastruktursatsningar inom NorthPopkonceptet som också presenterats av fd rektor Göran Sandberg vid det första planeringsmötet för den struktur vid VR som senare kom att bli BBMRI.se. NorthPop-konceptet ingick redan 2009 i den ursprungliga BBMRI- ansökan som en central komponent för att visa hur vi nyttjar genealogisk teknik inkl. flergenerationsregistret och biobanker. NorthPop barn kommer nu att starta under hösten 2014 efter ett omfattande planeringsoch förankringsarbete där flera enheter såväl inom landstinget som universitetet omfattas. Bland annat har ett flertal pilotförsök genomförts (olika tekniker för insamling av navelsträngsblod, tidsstudier av provhantering fram till dess att prover finns i frys etc). Se bilaga projektplan för det första tilltänkta projektet, allergisk sjukdom. Avsikten är att prover och data i möjligaste mån insamlas i enlighet med av BBMRI.se tillstyrkta, internationellt jämförbara kvalitetsstandarder . Avsikten är även att Northpop ska använda BBMRI:s IT-infrastruktur, Integrated Study Informatics Services. Ytterligare samordning förväntas med LifeGene på sikt. NorthPop kommer att vidmakthålla en öppen mekanism för att externa forskare ska kunna ansöka om uttag av prover och/eller data. Vad vi behöver är en oförändrad budget samt anslag till infrastrukturdelen. Infrastrukturbehovet är stort. Internationellt finns ingen motsvarighet till denna infrastuktur med en täckning av alla generationer med blodprover, expositionsdata och genealogier i en hel befolkning. Detta var tänkt som ett flaggskepp inom BBMRI.se och så kommer det att bli! 44 APPENDIX 3 Strengthening prospective cohorts in Sweden: the case of the Northern Sweden Health and Disease Study (NSHDS) SUMMARY The Northern Sweden Health and Disease Study (NSHDS) harbours unique resources and opportunities to conduct state-of-the-art studies on chronic diseases using prospectively collected baseline data and biospecimen. In order to increase the efficiency by which such studies can be conducted, and to capitalize on the structural resources available within Sweden and the Nordic countries, we propose that BBMRI.se support a number of activities within the NSHDS, centred around i) integrating data and access to clinical biobanks, ii), harmonization of baseline data, iii) building of IT infrastructure to allow centralization of omics data, and iv) adapting the description of resources and processes to ISO standardization. We argue that if BBMRI.se can further strengthen the existing and emerging infrastructure of prospective cohort studies in Sweden, there is an opportunity to create a research environment to study disease aetiology that is truly unique in an international perspective. BACKGROUND In studies of disease aetiology, it is becoming widely accepted in the field of observational epidemiology that population based prospective cohorts are necessary to obtain unbiased relative risk estimates of disease. Such cohort studies recruited healthy participants and collected exposure data and biological material at baseline, and subsequently followed the participants throughout their lifespan to identify the occurrence of disease. Because most diseases are relatively rare in the general population, such cohort studies must by necessity recruit very large baseline populations to obtain an adequate number of incident cases with disease and enable informative comparisons with healthy controls. The utility of any given cohort study is largely depending on i) its baseline sample size, ii) years of follow-up, and iii) quality of baseline data and biosamples. Highly cited cohort studies, such as the US Nurses Health Study (NHS, http://www.channing.harvard.edu/nhs/), typically involve 100s of thousands of study participants followed up for up to 20 years. RESOURCES AND OPPORTUNITIES IN SWEDEN In an international perspective, the Nordic countries, and Sweden in particular, have unique resources and opportunities to conduct state-of-the-art studies of prospective cohorts. These include important logistical advantages such as the ability to efficiently identify incident disease cases by use of the unique personal identifier and linkage with disease registries; the ability to efficiently identify fatal disease and overall mortality by use of the unique personal identifier and linkage with the cause of death registry; 45 The biosamples are frozen within one hour and taken in a fasting state, thus minimizing the impact of the intestinal microbiota. Important for some omic technologies, like metabolomics. The questionnaires are filled at the screening centre during the surveillance of the screening staff. well-organized pathology and cytology biobanks that offer the opportunity to link prospectively collected disease cases with subsequent disease tissue, and relatively small research community across the country that should facilitate collaborative scientific and infrastructure initiatives, such as the BBMRI.se. THE NORTHERN SWEDEN HEALTH AND DISEASE STUDY (NSHDS) The Northern Sweden Health and Disease Cohort (NSHDS) is unique worldwide in that the study participants have been recruited continuously since the 1980s through the local health care centres in Västerbotten. With over 110,000 study participants recruited to date, many followed for a period of over 25 years with multiple baseline measures, the NSHDS represents a rich collection of biospecimen and health data that is widely used for observational studies of chronic diseases. Limitations and corrective actions Despite the structural advantages of conducting a prospective cohort in Sweden indicated above, there are some practical obstacles, each highly relevant for BBMRI.se, that limit the rate by which innovative studies can be initiated within NSHDS. These include 1. Different versions of baseline questionnaires having been used through the history of the cohort, which makes studies where data from the entire cohort are sought slow and dependant on time-consuming and redundant data harmonization efforts. It also limits the possibility to participate in, and lead larger consortia where data and biospecimen from multiple prospective cohorts are used. 2. Lack of established routines for i) linking the cohort database with clinical biobanks (e.g. pathology biobank) and ii) granting access to disease tissues for NSHDS related studies. This makes the initiation of studies where prospective data and related disease tissues extremely time-consuming and administratively cumbersome. 3. Lack of routines and IT infrastructure for bringing data derived from the use of NSHDS biospecimen (e.g. genome-wide data) back to a centralized data base. 4. Need of updating/developing the GLP Quality manual for continuous control of resources and processes. Fortunately these limitations can be remedied by modest, but targeted investments. In order to improve the efficiency by which innovative studies can be carried out within NSHDS, and within the broader BBMRI community, we therefore propose earmarking resources within BBMRI.se for targeted process and quality work in Umeå focusing on the following components, 46 To link the NSHDS with the local clinical pathology and cytology biobanks at the Umeå University Hospital. This will require coordination support to clarify legal, ethical, administrative, and logistical obstacles for studying disease tissue for which prospective biosamples and data are available within cohorts. If Swedish prospective and clinical recourses can be successfully integrated, this may provide a resource that is truly unique in an international perspective. Umeå would also seem particularly suited to initiate this work in Sweden because the relevant disease tissues would, as a rule, be located on one single biobank, such as the clinical pathology biobank. To harmonize baseline exposure data, lifestyle information, and clinical information across all recruitment periods of the NSHDS. In particular we propose harmonizing the data from each recruitment period to the period of 1992-1996. Because the data from this period is already harmonized with the European Prospective Investigation into Cancer and Nutrition (EPIC) study, it would make further harmonization of the entire cohort to EPIC trivial, and greatly facilitate contributing to international consortia, such as the BBMRI-LPC and the NCI cohort consortium. It would also avoid time consuming, and often redundant, study-specific harmonization efforts obsolete. Establish routines for bringing data generated from the use of NSHDS biospecimen to a centralized database and build a flexible IT-infrastructure to harbour such data. Achieving an efficient mechanism to bring back such data, including (but not limited to) genome-wide genotyping data, metabolomics and proteomics data, as well as sequencing data, would greatly facilitate secondary use of such data, locally, as well as nationally and internationally. Updating the GLP Quality manual and adapting to existent/emerging ISO/TC 212/276 Standards for continuous surveillance of existing resources and processes. It would seem that each of these activities are of direct relevance for BBMRI.se in building a world-leading biobank infrastructure that capitalizes on the unique resources available within the Nordic countries, in particular in regards to available registries and centralized disease biobanks. 47 APPENDIX 4. Umeå 2014-09-22 Nationell samordning av immunitetsövervakning och biobanker för förbättrad nationell beredskap mot epidemier, biologiska hot och spridning av antibiotikaresistens Sverige har en icke utnyttjad resurs av material, data och kunskaper som med rätt infrastruktur kan användas för att förebygga framtida infektionshot En god nationell beredskap är central för att förhindra eller minimera konsekvenserna av epidemier och biologiska hot. En viktig komponent i en sådan beredskap vore ett rationellt utnyttjande av prover från existerande biobanker för att möjliggöra snabb prediktion av befolkningens mottaglighet för infektioner samt kartläggning av spridning av infektioner. Biobanker är gravt underutnyttjade men om det skulle finnas ett nationellt, allmänt sökbart register skulle sådana analyser snabbt kunna genomföras och den nationella beredskapen avsevärt förbättras. Detta skulle, t.ex., genom analyser av blodprover, ge ett nödvändigt beslutsunderlag för riskbedömning av epidemier och biologiska hot. Den stora mängden tillgänglig information kan även komma att klargöra mer komplexa, idag okända samband, t.ex. mellan genetiska komponenter som predisponerar för infektioner eller som kan kopplas till infektioners svårighetsgrad. Det finns även mycket stora mikrobiella provsamlingar i biobanker på universitet och sjukhus och den kan, om de görs tillgängliga nationellt, bli unika resurser för vår beredskap för att kunna kontrollera det idag snabbast växande medicinska problemet, antibiotikaresistens. Analyser av de mikrobiella biobankerna skulle ge oss essentiell information om förändringar av antibiotikaresistens och ge möjlighet att sätta in åtgärder i ett tidigt skede för att förhindra omfattande framtida spridning av antibiotikaresistenta bakterier, t.ex. den mycket snabba spridning som skett av de s.k. ESBL bakterierna under senaste decenniet. Det är noterbart att denna ökning har skett trots att det finns en strikt nationell policy för antibiotikaanvändning, vilket visar att sådana åtgärder i sig inte är tillräckliga utan att ytterligare nationella insatser är nödvändiga. En nationell samordning som gör att dessa mikrobiella biobanker kan kopplas till de serologiska biobankerna skulle dessutom ge ovärderlig information om faktorer som predisponerar för förekomst och spridning av antibiotikaresistenta bakterier, ett område där vår kunskap idag är mycket ofullständig. I detta förslag beskrivs hur de existerande serologiska och mikrobiologiska biobankerna kan användas för att ge ett verkningsfullt bidrag till en nationell handlingsplan för immunitetsövervakning samt spridning av antibiotikaresistens. Vetenskapligt nätverk: Anders Johansson, Näringsforskning Umeå Universitet, representerar projektet i BBMRI, WP2 Anders Sjöstedt, Klinisk Mikrobiologi, Umeå Universitet, vetenskaplig ledare Karin Tegmark Wisell, Mirobiologi, Folkhälsomyndigheten, Stockholm Björn Olse´n, Infektion, Akademiska sjukhuset, Uppsala Mats Forsman, FOI, Totalförsvarets Forskningsinstitut Göran Hallmans, Umeå biobank, Näringsforskning, Umeå Universitet 48 Handlingsplan 1. Uppbyggande av nätverk. Idag finns en nationell infrastruktur för insamlande och analys av biobanksprov från patienter och friska individer (BBMRI.se). Infrastrukturen ger möjligheter att snabbt få en översikt över de mer än 90 provsamlingar som finns registrerade (BBMRI.se Sample Collection Register). Samtliga medicinska fakulteter vid Sveriges lärosäten är även knutna till det europeiska biobanksprogrammet BBMRI. För att kunna utnyttja denna befintliga infrastruktur för immunitetsövervakning behövs ett vetenskapligt nätverk med kompetens inom biobanking, mikrobiologi, infektionssjukdomar, epidemiologi och statistik. Ett nationellt nätverk har formats bestående av forskare från Umeå Universitet, Uppsala Universitet, Karolinska institutet och Totalförsvarets forskningsinstitut, FOI. För att förstärka detta nätverk har kontakter även initierats med Folkhälsomyndigheten, som stödjer idén att använda biobanksprover i detta syfte. Detta skulle bli en viktig resurs för det nationella epidemiologiska arbete som Folkhälsomyndigheten ansvarar för. 2. Sammanlänkande av tillgängligt material lagrat i de olika nationella biobankerna. I anslutning till våra nationella biobanker finns en mängd provsamlingar vilka idag inte är fullständigt kartlagda och därför inte tillgängliga för individer utanför den egna forskargruppen. Detta material innehåller både mikroorganismer och serum från infekterade individer, varför det är av stor vikt att kartlägga och synliggöra dessa material. Ett undantag i detta avseende är Uppsala biobank, som har inkorporerat i stort sett alla lokala provsamlingar under ett och samma register (www.uppsalabiobank.uu.se). Vår avsikt är att med detta som förebild utföra ett liknande arbete i övriga Sverige för att göra biobankerna allmänt tillgängliga och sökbara, vilket inkluderar både de mikrobiella biobankerna och de biobanker nationellt som passar in på immunitetsbiobankens kravspecifikation. 3. Kartläggning av biobanksmaterial i Sverige av infektionsmedicinsk relevans. Biobanker spelar en central roll för medicinsk forskning då de tillåter analyser av riskfaktorer som predisponerar för sjukdom och förändringar som sker hos patienter under loppet av tiotals år innan sjukdomar kliniskt kan diagnosticeras. Detta har i många fall revolutionerat vår förståelse för patogenesen vid många sjukdomar, tex 49 kardiovaskulära sjukdomar, cancer och autoimmunitet. Biobanker har däremot inte utnyttjats på samma revolutionerande sätt när det gäller förståelsen av klassiska infektionssjukdomar. En orsak är naturligtvis att de flesta infektionssjukdomar är akuta och därför existerar inte predisponerande faktorer på samma sätt som för de tidigare nämnda sjukdomarna. En annan faktor är att kopplingen mellan epidemiologisk forskning och infektionsforskning historiskt varit relativt svag i Sverige. Vi ser detta som en uppenbar svaghet för vår nationella beredskap både kortsiktigt och långsiktigt. Det finns ett flertal viktiga exempel på nyttan att kunna använda biobanker ur ett kort tidsperspektiv; ett sådant är det återkommande hotet som säsongsinfluensa innebär. De årliga utbrotten orsakar en markant säsongsberoende överdödlighet hos befolkningen, i första hand hos äldre individer, vilket naturligtvis är ett starkt incitament för vaccination. Problemet är att tidigt kunna producera ett vaccin med de rätta immunogena egenskaperna och även snabbt få kunskap om hur immunitetsläget är i befolkningen. I det senare fallet finns en uppenbar och central roll för att snabbt få tillgång till relevanta sera från individer i olika åldrar och från olika delar av Sverige. Om det nationellt skulle finnas register över sera som tagits i närtid och är tillgängliga i olika delar av landet skulle immunitetsläget kunna kartläggas inom ett par veckor. Ur ett långsiktigt perspektiv så finns det ett flertal exempel på hur viktigt det är att över tiden analysera förändringar hos mikrober och av immunitetsläget nationellt. I det förra fallet är de s.k. ESBL bakterierna ett slående exempel. Detta begrepp myntades för bara 20 år sedan och innan dess hade dessa bakterier varit mycket sällsynta. De är Gramnegativa bakterier som har en utomordentlig förmåga att bryta ner de flesta beta-laktam antibiotika vilka rutinmässigt används vid behandling av både mindre allvarliga och allvarliga infektioner. Ett tydligt exempel på de problem som förekomsten av ESBL bakterier medför är att patienter med urinvägsinfektioner orsakade av ESBL bakterier inte säkert kan behandlas peroralt utan det kan krävas intravenös behandling vilket på ett dramatiskt sätt ökar vårdkostnaden. Sedan ESBL bakterier blev rapporteringsskyldiga 2007 så har det skett en fyrfaldig ökning av antalet fall med idag >8000 fall/år och de utgör därmed det enskilt största problemet när det gäller antibiotikaresistens. Utifrån denna bakgrund ser vi att det finns ett stort och brådskande behov av en nationell plan för att samordna utnyttjandet av existerande biobanker. I det här avseendet används beteckningen för att inkludera samlingar av sera samt av bakterier och virus. Vi ser att de förra skulle kunna utnyttjas för att snabbt kunna inventera immunitetsläget nationellt vilket skulle ge mycket viktig information om risker för att utbrott av större epidemier. Det ovan beskrivna exemplet med influensa kan vara ett exempel på ett behov av denna resurs men det finns också relativt många exempel på andra infektionssjukdomar som inte är lika vanliga men som tidigare har gett upphov till större utbrott, t.ex. kikhosta och 50 streptokockinfektioner. En sådan beredskap skulle kräva att det finns ett nationellt register där sera som både insamlats nyligen och tidigare är sökbara samt att dessa snabbt kan distribueras för att analyseras. När det gäller biobanker som innehåller samlingar av bakterier och virus så kan dessa bli essentiella för ett framgångsrikt vårdhygieniskt arbete i syfte att förhindra smittspridning inom vården. Idag finns möjligheter att genetiskt identifiera mikrober så att smittspridning av riskpatogener kan följas med extrem precision vilket kan leda till förbättrade strategier för begränsning av smittspridningen. Vidare är sådan kunskap, inklusive information om historiska isolat, av central betydelse för att förstå mekanismerna bakom den katastrofala spridning av ESBL bakterier som vi ser idag. Detta resonemang utvecklas ytterligare under punkt 4 nedan. Vi ser även att mer komplexa samband kan klargöras om en nationell samordning mellan mikrobiella och serologiska biobankerna finns. Ett exempel är att det skulle kunna identifiera värdfaktorer som predisponerar för förekomst och spridning av antibiotikaresistenta bakterier, ett område där vår kunskap idag är mycket ofullständig. Ett annat område där ett effektivt utnyttjande av biobanker kan kopplas till värdfaktorer gäller förståelsen av genetiska komponenter som predisponerar för infektioner och som även kan kopplas till infektioners svårighetsgrad. Det är sannolikt att det redan idag finns lokala biobanker av tillräcklig omfattning för att studier kan adressera de tidigare nämnda frågeställningarna. Biobanker av intresse för infektionsområdet har skapats huvudsakligen av två orsaker, det ena är att en väl fungerande klinisk diagnostik kräver tillgång till historiska sera från patienter som insjuknat i någon infektionssjukdom. En serologisk diagnos får en mycket större precision om ett akutserum kan jämföras med ett tidigare taget serum från samma patient. Därför finns det serologiska banker som i vissa fall omfattar 100,000-tals prover vid vissa kliniska laboratorier. Den andra orsaken är behovet att bättre förstå smittspridning vilket är av intresse både kliniskt och forskningsmässigt. Det finns därför biobanker på universitet och sjukhus som innehåller tusentals mikrober som insamlats under loppet av flera decennier. Dessa mikrobiologiska biobanker har idag en ännu större potential än tidigare då våra möjligheter att analysera mikroberna är mycket bättre pga tekniska landvinningar som tillåter fullständiga genomanalyser till mycket överkomliga kostnader. Problemet är att många av de beskrivna biobankerna inte uppfyller kraven på full sökbarhet samt snabb distribution. Det finns ingen fullständig inventering av alla tillgängliga biobanker samt ingen lättillgänglig information om innehållet och hur snabbt man kan få ut ett prov. Vidare så är det få av dessa som har en etablerad infrastruktur som tillåter att sera på ett snabbt och effektivt sätt kan distribueras. Dessutom behöver det i förväg upprättas ett regelverk kring åtkomsten till dessa biobanker så att inte formella skäl förhindrar ett snabbt utnyttjandet. 51 4. Framtida insamling av av mikroorganismer och sera. Utifrån resonemanget under punkt 3 så drar vi slutsatsen att det finns ett tydligt nationellt behov av en organiserad framtida insamling av mikrober kopplat till en systematisk kartläggning av klonalitet hos mikroberna, deras resistensmönster och klinisk relevans samt samtidig insamling av blod och sera från de aktuella patienterna som kan användas för att ge oss en förståelse för de mer komplexa sambanden som t.ex. genetisk predisposition för infektionssjukdomar samt bärarskap av antibiotikaresistenta bakterier. Från ett epidemiologiskt perspektiv vore det rimligt att ett begränsat antal laboratorier med god geografisk spridning identifieras för att ansvara för detta insamlande. Dessutom ska ett krav vara att laboratorierna har tillgång till historiska material vilka ska göras tillgängliga för att jämföras med det som kommer att insamlas i framtiden. Vidare ska en forskningsmässig komponent ingå i detta ansvar så att laboratorierna kontinuerligt karakteriserar de insamlade isolaten med avancerad metodologi och analyserar denna information tillsammans de andra ansvariga laboratorierna så att en ständigt uppdaterad epidemiologisk information finns tillgänglig. I Sverige återfinns, om än sporadiskt, höggradigt smittsamma mikrober. En större spridning av sådana utgör en samhällsfara. Ett exempel är mjältbrand som har orsakat utbrott hos boskap 2008 och 2011 och ytterligare exempel är Francisella, Brucella och Coxiella. Flera av dessa organismer anses utgöra potentiella bioterrorismhot. Ett sätt att förbättra beredskapen mot sådana hot är att i det skisserade nationella nätverket skapa ett system för att karakterisera alla isolat med avancerad metodologi, vilket skulle möjliggöra tidig upptäckt av ovanliga mönster i deras spridning och snabbt insättande av åtgärder. 5. Handlingsplan för snabb insamling av nytt provmaterial vid utbrott Betydelse Den ovan beskrivna verksamheten kommer att avsevärt förbättra beredskapen i Sverige och därigenom minimera effekterna av infektionsmedicinska risker, t.ex. epidemier, nya biologiska hot, eller infektionssjukdomar som sällan eller aldrig idag förekommer i Sverige. Flera av dessa risker kommer sannolikt att öka i framtiden p.g.a. av den ökande globaliseringen och klimatförändringarna som gynnar smittspridning, vilket är ytterligare argument för en förbättrad beredskap. En sådan beredskap kommer att ge oss kraftfulla verktyg för att i realtid kunna identifiera nya utbrott och för att minimera deras följder. Dessutom kommer en sådan kunskap att ge oss unik information om de aktuella, allvarliga problem som vi idag har inom det infektionsmedicinska området, ffa med antibiotikaresistens, för att långsiktigt på ett bättre sätt kunna hantera dessa. 52 APPENDIX 5 The National Environmental Sample Biobank (NHMB) A network will be created within BBMRI.se on environmental health studies in biobanks. Each part of BBMRI.se will be asked to appoint one representative. Additional guests, though maybe a limited number, will be welcome to network meetings. This network will facilitate scientific exploration of biobank samples. In addition, the network will form a scientific correspondent to the already existing network of NHMB, which includes Swedish authorities involved in environmental issues (Environmental Protection Agency, Food Agency). A first meeting will be held spring 2015. A study set will be set up within VIP for time-trend studies of chemicals and environmental pollutants. The set will also facilitate other time-trend studies and researchers of all disciplines will be invited to access samples. The design is yet to be defined, but will most probably be relatively small and include repeated samples from the same individuals, in order to assess within-individual variation. In addition, we will explore if a test set for within- and between-individual variation should be created (to be used for example when calculating statistical power when novel biomarkers are to be used, both within the environmental field and within others), and begin discussions of how different samples matrices (blood, plasma, urine, nails, etc.) can be studied in future biobank studies. 53 APPENDIX 6. Kort sammanfattning för bbmri.se om arbetet med DEMOS-projektet DEMOS: Vitamin D and Epstein-Barr virus – Infectious Mononucleosis – in Multiple Sclerosis etiology De första kontakterna med virologbiobanker i Sverige togs våren 2012 och den första samkörningen med den nationella MS-databasen med över 11000 personer gjordes sommaren 2012 (Skåne biobank och SMI). Samkörning har sedan gjorts med samtliga virologbiobanker knutna till universitetssjukhus (dock ej KS), samt SMI/Folkhälsomyndigheten. Projektet är godkänt av styrgrupper (inkl KS:s) för samtliga biobanker (och EPN med kompletteringar, Svenska MS-registrets forskningsnämnd, samt Datainspektionen). Det totala antal prover i dessa biobanker uppskattas till preliminärt till 2500000, och vi håller på med att karaktärisera dessa biobanker m a p antal prover, ålder vid provtagning, provtagningsår etc. Prover från fall har i normalfallet validerats av lokalt arbetande neurolog med avseende på diagnos, förloppstyp och debutdatum – de prover som har inkluderats är från personer som senare utvecklat prototypisk MS. Arbetet med att identifiera matchade kontroller är avslutat på tre biobanker (Göteborg, Skåne och SMI) och på dessa tre ställen är provplockning klar om 2 veckor. Att projektet hunnit längst här beror inte enbart på att projektet kom igång tidigast på dessa tre ställen. På Folkhälsomyndigheten/SMI och Skåne har personalen erfarenhet av liknande projekt, och i Göteborg finns sedan tidigare ett etablerat forskningssamarbete mellan virologer och neurologer. I Umeå kommer matchade kontroller selekteras ffa manuellt sommaren 2014. I Uppsala har prov lämnade innan 2007/8 kasserats och samkörningen resulterade endast i ett enda säkerställt prov. Identifiering av kontroller pågår i Linköping och Örebro (Se tabell nedan). Alla mina kontakter har skett mail- och telefonledes och har innefattat kontakt med företrädare för styrgrupper/chefer, biobanksansvariga, representanter för bbmri.se, statistiker/IT-ansvarig, BMA på virologlab och lokala neurologer. Personuppgifter där personnummer har använts har skickats via rekommenderat brev i kodad och krypterad form. Svårigheterna har varit relativt jämnt fördelade inkluderande min egen begränsade tid - har endast haft 20% forskningstid, vilket dock utökas fr o m i höst. Upplevelsen är att insatser från många involverade har gjorts på övertid eller när en lucka funnits. Arbetet har därmed ofta haft karaktären av det lågbudgetprojekt som det hittills varit! Projektet är omfattande med flera planerade analyser och EPN-ansökan är bredare än DEMOS-projektet, vilket innebär att det för en oinvigd inte varit helt enkelt att sätta sig in i projektet. Arbetet med att identifiera matchade kontroller har nog varit svårast. Har krävts ett lokalt producerad script, som bl a behövt inkludera matchning för subkohorter i biobanker. På två biobanker saknas möjlighet att göra datassökning i virologisk databas (KS, samt delvis för Umeå). Som väntat har en mindre andel av prover som ska finnas enligt databas inte återfunnits i frysen. Förhoppningen inledningsvis var att hitta 1000 prospektiva MS-prover och den siffran kommer vi uppnå när vi adderar vår tidigare pilotstudie. 54 Aktuellt status för DEMOS-projektet: Samkörning Umeå Göteborg Skåne KS SMI Uppsala Linköping Örebro Klar Klar Klar Nej Klar Klar Klar Klar Prospektiva MS-prover enligt samkörning 134 65 414 Antal prov i frys bekräftat Validering av prospektiva fall Identifiering av kontroller Prover skickade 49 (359) Klar Klar Klar Pågår Klar Klar Ja Juni 2014 210 1(-3) 105 62 (175) Delvis gjord Klar Pågår Pågår Klar Juni 2014 55 Pågår APPENDIX 7. Nationella Biobanksbaserade Infrastrukturer: rapport 2013 Nyskapade nationella infrastrukturer, inkl. användare Ett centralt mål för BBMRI.se är att främja att Sverige skall behålla och vidareutveckla sin ställning som en ledande nation inom den internationella biobanksforskningen. BBMRI.se, arbetspaket 2 (WP2) har arbetat med att aktivt tillgängliggöra befintliga biobanker för nationellt samordnade forskningsprojekt samt i vissa fall med utveckling av nya biobanker enligt fastställd utvecklingsplan. Avsikten är att genom nationell samordning av befintliga biobanker stimulera forskare att skapa den största federerade biobanken i världen som effektivt kan utnyttjas för forskning, främst genom att nya infrastrukturer tillskapas som kan återanvändas för nya frågeställningar. Exempel på skapade infrastrukturer, metodstudier m.m. framgår nedan under särskilda rubriker som nu uppdaterats med resultat från 2013. Beträffande serumbiobankerna nyttjas nu flertalet med MS projektet som ”plog”. Undantaget är Stockholm där serumbiobankerna (frånsett SMI) ej är åtkomliga i praktiken. Att så inte blir fallet framgent blir en uppgift för organisationen i Stockholm: Nyskapade infrastrukturer av internationellt ledande karaktär1 Projekt PI/Forskare Orter Antal prover/ motsvarande MetaHealth Subarachnoidalblödningar Johan Sundström Hela landet Uppsala koordinerar 890 000 (kohort) 1 Status 2014-01 EPN-godkännande. Data från 23 svenska populationsbaserade kohorter är insamlade. Länkning av 5 av kohorter mot de offentliga registren pågår sedan mitten av 2013. Harmonisering av variabler i de olika kohorterna pågår. Piloten och arbetsprocessen kommer noga utvärderas innan Världsledande i enlighet med VR:s deklaration (huvuduppgift för WP2) måste tydligt definieras, från fall till fall och får redovisas separat. Ofta tillskapas större prospektiva forskningsmaterial än de som tidigare funnits internationellt, i andra fall finns nya komponenter av stort vetenskapligt värde. 56 Rheumatoid Artrit (PreRA) MS Riskfaktorer för multipel skleros med fokus på körtelfeber Proj. 1: Johan Askling Stockholm, Falun, Göteborg, SMI, Proj. 2: Solbritt RantapääDahlqvist Umeå Peter Sundström Umeå koordinerar deltagande biobanker (universitetssjukhusen och SMI) Samkörningar pågår nationellt på serumbiobanker (ca 2 500 serumprover) Proj. 2: Ca. 1 900 serum- och plasma prover 164 000 (kohort) Samkörningar pågår nationellt. Skattad totalmängd fall: 1 000. Matchning kontroller 1:1. En rad analyser planeras, bl.a. Illuminexanalys av olika EBV-ak, JCvirus mm baserad på analys av 2 uL, fortsättning med andra sjukdomsområden. Proj. 1: Pågående. Materialen i insamlingsfas. Samarbete WP6. Upprättande av sekundär biobank. Proj. 2: Pågående arbete i primär biobank. Samkörning gjord: Umeå: 100 säkerställda men sannolikt uppåt 200 prospektiva fall, sammanställning pågår (+ sed tidigare data för 192 fall+384 kontroller som kan poolas) Skåne: 480 prospektiva fall, ska dubbelkollas av neurolog i Malmö. SMI: 269 prospektiva fall, ska dubbelkollas. Göteborg: 5 000 prover från drygt 1 300 personer, identifiering av prospektiva fall pågår av neurolog i Gbg Samkörning/uttag godkänt: KS: Samkörning planeras parallellt med pre-RA projektet (Askling m fl) Uppsala: Har erhållit MS-data fil. Linköping: Samkörning slutförd. Komplett genetik finns på ca. hälften av fallen. Det blir en utmaning att selektera kontroller om så skall ske, ett par varianter finns för detta om projektet kan genomföras. 57 ALS PI: Epidemiol. Weimin Ye Stockholm, Malmö SjukdomsUmeå specifik PI: Peter Andersén 253 registrerade från två serumbiobanker (Skåne + SMI). Insamling pågår från övriga biobanker Pågående. Nationell samordning. 6 200 expositionsdata + DNA + plasma För GWAS 4 000. Replikerats i Womens Health Initiative (WHI) 25 års uppföljning. Betula biobank: 4 000 prover. Pågående. EPN godkännande 2010/2011. Data från UFO (Umeå) men med tiden även från Mr OS . Cirka 2 500 frakturfall i UFO, majoriteten prospektiva. Första arbetet är submitterat. Världsledande material. Genetiska studier av Osteoporos/ frakturer Claes Ohlsson Ulrika Petterson Kymmer Göteborg, Umeå Betula: Longitudinell studie av åldrande, minne och demens http://w3.psychol ogy.su.se/betula/ medarbetare.html Lars Göran Nilsson, Rolf Adolfsson, Lars Nyberg Stockholm Tumörmaterial kopplade till prospektivt insamlade blodprover: Njurcancer Börje Ljungberg Umeå Ca 800 med kliniska data, blodprover och tumörvävnad. 120 prospektiva fall, dvs de har blodprov i Medicinska biobanken före antingen diagnosdatum i ca.reg eller före operationsdatum Tumörmaterial kopplade till Malin Sund Umeå 1. Bröstcancer 700 fall. Umeå 58 Deltagarna har testats, intervjuats och undersökts medicinskt och psykologiskt vid fem tillfällen (1988-90, 1993-95, 1998-2000, 2003-2005 och 2008-2010). Samordning med meabolomicsprojekten i Umeå biobanken samt två EU-projekt (CHANCES + ansökan om depressioner). Insamling av blod och tumörmaterial har systematiskt pågått sedan mitten på 80-talet. Internationellt unikt stor biobank som nu samordnas med NSHDS (prospektivt insamlade prover och data) . Internationellt ledande material, både till storlek, kvalitet och uppföljningstid. 1. Bröstcancer sedan 1997 Validering Malmö. prospektivt insamlade blodprover: Bröstcancer och pancreascancer Fullständig klinisk databas. Prospektiv insamling (plasma och serum) vid diagnos (tumören kvar), 6-8 veckor postoperativt samt vid 1 år alternativ relaps av sjukdom. Dessa sparas i -80C i Umeå bröstcancer biobank. Dessutom skärs vävnadsprover från tumören samt frisk vävnad vilka sparas färskfruset i -80C. 2 a. Pancreas2a. Pankreascancer sedan 2009 cancer. Omfattar ca 120 Plasma och serum) vid diagnos fall. Fullständig (tumören kvar), 6-8 veckor klinisk databas. postoperativt samt vid 1 år alternativ relaps av sjukdom. Dessa sparas i -80C. Vävnadsprover från tumören som sparas färskfruset i -80C. Malin Sund, Jonas Manjer Tumörmaterial kopplade till prospektivt insamlade blodprover: Ovarialcancer Eva Lundin, Annika Idahl 2b. Pancreascancer. 167 fall med prediagnostiska prover kan användas för tidig detektion av pankreas cancer med fullständig klinisk databas DiskussDet finns 260 ioner pågår individer med om samord- blodprov vid ning med diagnos innan UCAN behandling Umeå/ som dessutom Uppsala. har ett eller flera prospektiva blodprover i 59 2b. Prospektiva prover Pancreascancer – Northern Sweden Health and Disease Study Ett samarbete är initierat med Malmö kost och cancer- kohort inom ramen för detta projekt. Där finns en liknande kohort vilket möjliggör validering av fynd i Umeå-kohorten. Detta är det första systematiska projektet med insamling av blodprover vid diagnos för att specifika titerstegringar av selekterade markörer m.m. skall kunna användas för tidig diagnos av ovarialcancer. Olika projekt har initierats inom området. Insamlingen fortsätter av alla fall som kommer till universitetssjukhuset i Umeå, NSHDS. samordning sker med NSHDS. Antal med tumörvävnad ska kontrolleras. Tumörmaterial kopplade till prospektivt insamlade blodprover: Colorectal cancer (CRC) Richard Palmquist, Ingrid Ljuslinder UCAN, samarbete Uppsala, Umeå. Tumörmaterial kopplade till prospektivt insamlade blodprover andra cancerformer som prostata, lunga m.fl. Mikael Johansson, Kjell Grankvist, Pär Stattin, Börje Ljungberg + fler personer inom UCAN. Umeå Blod och Tumör- och blodprover från patienter som ingår i UCAN – provinsamling, kombinerat med prospektivt insamlade prover. Det finns ca 1000 fall (350 i Umeå, varav 150 har prospektiva prover i Medicinska biobanken) Regional organisation klar för lungcancer. Provinsamling påbörjad (72 patienter med blodprover + tumörmaterial på 27 patienter). Prostata ca 500 unika fall med provtagning vid diagnos (biopsi 60 Till detta projekt utnyttjas UCAN kombinerat med prediagnostiska blodprover från den omfattande provinsamlingen i den Medicinska biobanken. Samordning sker också med Uppsala och det finns en viss finansiering inom UCAN för specifika projekt. Sammanställningar pågår. Dessa material är även internationellt ledande, beroende på att andra länder i allmänhet inte har dessa möjligheter. Malmö har i dessa fall samma möjligheter som Umeå, och där finns många material som vi inte arbetat med inom WP 2 men som v.b. kan dokumenteras i framtiden. Beträffande prostata och blåscancer förväntas en stor del finnas matchade till prospektiva prover i Medicinska biobanken. + blod), på motsvarande sätt blåscancer 400. Prostatacancer: ” Analys av PSA och kallekreiner som prediktorer av prostatacancerdöd” Pär Stattin, Hans Lilja Umeå, Malmö. 3 000 fall 6 000 kontroller. Metabolomicsprojekt för tidig diagnos och patogenes av cancer och Alzheimers sjukdom Vaskulit - Prediktiva faktorer för senare utveckling av vaskulitsjukdom hos symptomfria individer. Metabolomicsgruppen och tumöransvariga i Umeå + Ali Ata Moazzami, Uppsala Solbritt Rantapää Dahlqvist, Ewa Berglin, Aladdin Mohammad Umeå, Uppsala, Prostatacancer, Pancreascancer, Alzheimers sjukdom. Umeå, Malmö samt biobanker i hela landet. >5 000 fall identifierade av SoS. Samkörningar planerade med serumbiobanker Identifiering av fall från Socialstyrelsen klart. Arbete pågår med att klarlägga ett bra arbetsflöde mellan forskara, biobankerna samt landstingen m a p samkörningar, journalrekvirering och provplockning ut frysarna. Linköping: Samkörningar pågår. NorthPop: Västerbotten imputation Paul Franks Claes Ohlsson, Frida Umeå, Göteborg, Uppbyggnad av en databank En genealogisk databas som är under uppbyggnad kommer att användas för att genomföra Samarbete WP2 och WP4. 61 Prediktion av risk för prostatacancer med hjälp av PSA värden och genetisk information, speciellt kopplad till kallikreinomsättningen vid olika åldersintervall (40,50,60) i populationsbaserade kohorter. Världens största prospektiva populationsbaserade material inom området, stöd från NCI. NIH/NCI (1R01CA16081601A1) (PI: Lilja) 08/01/2012 – 07/31/2013. Project title: Prospective validation of a multi-marker prostate cancer prediction model. Abstract inskickat tillASCO, publication snart inskickat till NEJM. Projektet på pancreascancer sker parallellt med ett liknande projekt inom EPIC. Alla tre projekten berör även metabola faktorer. databank of near-complete genomes (VIKING) Aortaaneurysm (NorthPop AAA) Renström Anders Brändström m fl. Malin Sund. Anders Wanhainen, Paul Franks Lund Cambridge. Umeå, Uppsala, Lund. IBD EPIC och non EPIC i Sverige Pontus Karling, Johan Söderholm Diskussioner - Umeå, Linköping GLIDE: Gene-Lifestyle Interactions in Dental Endpoints Ingegerd Johansson, Paul Franks, Dmitry Shungin, Pernilla Malmö/ Lund, Umeå, nationella kohorter. (>60 000 individer) med en nästan komplett kartläggning av genomet samordnat med demografiska data, livsstilsdata samt biokemiska data från främst VIP- kohorten. Projekt 1: 450 prover tillsammans med NorthPop 70. Samordning med VIP + genealogier. Projekt 2: 619 prospektiva blodprov från individer som senare utvecklat aortaaneurysm. Etikansökan godkänd. Oklart antal fall i serumbiobanker 10 svenska kohorter deltar med genetiska och metabola data som har länkats till 62 genomisk imputering. Kohorten kommer att bli den största som finns idag på en enskild, homogen befolkning. Ett pilotprojekt pågår på aortaaneurysm och sudden death, se separat rubrik. Studien innefattar återanvändning av ett flertal GWAS material. Anslag från VR och VINNOVA beviljat. Ansökt sökt från Wallenberg till ett uppdaterat projekt. Projekt 1. Prevalensen AAA har minskat dramatiskt under VIP projektperioden. Nu planeras ett genealogiskt inriktat projekt i samarbete med Sanger Institute. Projekt 2. Aneurysm lokaliserade till olika delar av aorta ffa thorakala aorta (TAA) och bukaorta (AAA). Klinisk databas. Etiologi och patogenes till AA studeras. Projekt görs i samarbete med Uppsala universitet. Pågår inom EPIC via ett internationellt ledande material, Planeringsfas i Sverige kopplad till serumbiobanker, vilket innebär att även yngre personer, som är den viktiga målgruppen, kan studeras. Samordning pågår mellan Sverige och EPIC. Den vetenskapliga processen med nyttjande av kohorten är i full gång med VR-anslag. Återanvändning av GWAS material från UFO och Glioma projekt Lundberg Paul Franks Olov Rolandsson, Peter Nilsson. InterAct Diabetes NorthPop: Why do some women with HPV-infection get cervical cancer while other do not? Paul Franks var med och grundade InterAct tillsammans med Nick Wareham Joakim Dillner, Johanna Ekström, David Lindquist Lund Umeå EPIC nationella dentala data till världens största kohort inom området. Kohort med DNA, erthrocyter och plasma, 24 000 individer. Umeå, Stockholm, Malmö Hög vetenskaplig aktivitet med återutnyttjande av det insamlade materialet, som nu öppnas upp för forskare utanför EPIC. En liknande diskussion pågår för hela EPIC. Projekt under uppbyggnad Registersamkörningar pågår. Kohorter med aktiv rekrytering av internationellt ledande karaktär2 Projekt LifeGene PI/Forskare Nancy Pedersen Orter Nationellt projekt med deltagande av Antal fall med prover 33 000 deltagare registrerade varav 20 000 har 2 Status 2014-01 Avbrott i insamlingen av prover av juridiska skäl. Engagemang från WP2 i den Världsledande i enlighet med VR:s deklaration måste tydligt definieras, från fall till fall och får redovisas separat. Ofta tillskapas större prospektiva forskningsmaterial än de som funnits tidigare internationellt, i andra fall finns nya komponenter av stort vetenskapligt värde. 63 Karolinska institutet samt universiteten i Lund, Umeå, Uppsala, Linköping, Göteborg WP 6 insamling deltagit, samt 25 000 har lämnat kompletta baslinjeunder sökningar. juridiska processen via media, forskare samt till jurister under 2012. Forskningsfasen har påbörjats med ett antal beviljade projekt. Lagreglering är nu klar och LifeGene kan återuppta sin verksamhet. EpiHealth Peter Nilsson, Lars Lind, Malmö/Lund Uppsala WP6 insamling 12 400 undersökta personer (Uppsala och Malmö/Lund). Insamling av prover pågår. Nationell kostkoordinering inledd via nationella möten. LifeGene Gravidstudie PI: Nancy Pedersen Stockholm WP 6 insamling Danderyds sjukhus och Södersjukhuset (SÖS) De första barnen som fötts i Gravidstudien har nu hunnit fylla ett år, dvs. ca 100 st. Prover från pilotstudie. LifeGene gravidstudie är en studie med eget etiskt godkännande vilket innebär att rekryteringen kan fortgå som vanligt. Pilotprojekt genomfört i Norsjö. 450 prover har tagits som en testomgång i Pilotprojektet kopplad till Aortascreening. LifeGene/EpiHealth frågor testade av personalen. Planering ålderspecifika frågor; kognitiv funktion, Operativ chef: Kicki Kjaergaard Northpop: Barn NorthPop 70 Magnus Domellöf, Christina West, Per-Åke Holmgren, Sven-Arne Silfverdal,Wareh am N, Paul Franks Stödorganisation: Göran Hallmans, Gerd Johansson Ulrika Pettersson Kymmer, Gerd Johansson Umeå, Lund Nationellt tillgänglig. Umeå 64 Pilotstudier genomförd med insamling av navelsträngsblod. Samordning med LifeGene och Morbarn-kohorten i Norge. Etikansökan inlämnad, men skall justeras. Intensiv uppbyggnadsfas med lokalt tillförda medel. anslutning till aortascreening. NorthPopKohorten Göran Hallmans Västerbotten, Norrbotten Koordinator av olika kohorter. Scapis Göran Bergström Pilot Göteborg Nationellt projekt planerat. Ca. 60 000 personer inom Norrlands biobanker där genealogier kommer att finnas. Norra länsdelen i Västerbotten klar samt vissa kommuner i Norrbotten. 1 000 blodprover insamlade i en pilot. WP 6 insamling Västerbottenskohorten (VIP kohorten) Göran Hallmans, Lars Weinehall, Åsa Ågren, Per Lenner, Ingegerd Johansson, Mats Nilsson, Margareta Norberg, Bernt Lindahl, Västerbotten Ca 100 000 individer, aktiv rekrytering pågår av ca 6 000/år, varav många tidigare deltagit, (ca 40 000 individer) 65 smärttillstånd i muskler, skelett och leder EpiHealth/LifeGene metoden för expositionsmätningar testad. P.g.a. medelbrist har planeringen stannat upp, och delvis tagits över av MONICA-projektet Specifika anslag avsatta från Umeå universitets styrelse för uppbyggnaden av genealogier. En komplettering kommer senare att ske med NorthPop 70 samt NorthPop barn. Projekt har påbörjats om familjär cancer (Beatrice Melin), trangenerationseffekter av graviditeter vid bröstcancer (PI Per Lenner)samt Viking infrastruktur (se speciell rubrik, PI Paul Franks) Pilot genomförd. Fortsatt rekrytering påbörjad i Göteborg, Malmö/Lund-site öppnar snart, övriga sites inväntar finansiering. Samarbete med WP6. Stor. Målsättning nationellt 30 000 individer. Samordning med befintliga kohorter. Mycket aktiv forskningsfas. MONICA U-CAN (UppsalaUmeå Comprehensive Cancer Consortium) Kurt Boman,m.fl. Stefan Söderberg Mats Eliasson m.fl. PI:s: Bengt Glimelius, Richard Palmquist Forskare: Ingrid Ljuslinder m fl. Norr- och Västerbotten samt även nationellt Ny screening 2014 med prover och enkäter från ca 1 600 deltagare, populationsbaserade från Norr- och Västerbotten. Uppsala, De två Umeå, sjukvårdsregionKTH er som ingår i Stockholm, projektet Programråd, omfattar en Programberedtredjedel av ning, exekutiv Sveriges grupp samt befolkning, där arbetsgrupper cirka 6 000 med särskilda patienter varje år ansvarsområden. nydiagnostiseras med de cancerdiagnoser som prioriteras i projektet. Många studier har utförts utifrån tidigare utförda screeningar både lokalt och nationellt. Planeringsarbete har pågått under 2013 Ny screening har påbörjats för vårvintern 2014. U-CAN samlar in och organiserar prov som tas från patienter före, under och efter cancerbehandling. Information om patienterna och röntgenbilder samlas också in. Målsättningen är att samla in färskfruset material från minst 95 % av tumörer i U-CAN:s målgrupp (gliom, prostatacancer, kolorectal cancer, lymfom/leukemier, neuroendokrina tumörer, gynekologisk cancer) och säkerställa att information om minst 98 % av patienterna förs in i kvalitetsregister. Nya ”tumörgrupper” söker nu om ”associering” beträffande insamlingsrutiner. Örebro förväntas ansluta sig till proj. Samarbeten i internationella konsortier samt nordiska kohorter3 3 Svenska forskare har ledande ställningar i EPIC, alla redovisade nordiska projekt, uppföljningen av Morgam som nu görs med provanalyser på ett stort material, ICPH, LC3, Kidrisk, HNC3, GliomaScan, GIANT, MAGIC, GLGC, CHARGE, GEFOS/GENOMOS 66 De svenska biobankerna är aktiva i uppbyggnaden av internationella konsortier, som krävs för att visa viktiga frågeställningar skall kunna besvaras. De första konsortierna har i allmänhet koncentrerat sina aktiviteter på genetiska studier, men nu börjar även gen-miljö interaktionsstudier utvecklas, vilket för att uppnå framgång ofta kräver mycket stora material. Projekt PI/Forskare Orter/ länder Antal prover/ motsvarande EPIC, The European Prospective Investigation into Cancer and Nutrition Jonas Manjer, Malin Sund, Mattias Johansson, Göran Hallmans. 23 centra, 10 länder. I Sverige: Malmö, Umeå. Danmark och Norge deltar också. Kohort, 520 000 individer, blodprov från >400 000. 10 länder deltar i Europa, 23 centra MORGAM, (MONICA, Risk, Genetics, Archiving, and Monograph; www.ktl.fi/morga m Kontaktpersoner,Sveri ge: Finland, Danmark, Sverige, Litauen, Polen, Ryssland, Nordirland, Frankrike, Skottland, Wales, Österrike. Kohort 128 874 individer. International Consortium on Pregnancy and Health (ICPH). PI Paolo Toniolo, USA. Annekatrin Lukanova, Umeå och Sverige Finland The Finnish Maternity Cohort (FMC) startades 1983. Innehåller serum från 98 % PG Wiklund, Stefan Söderberg Status 2014-01 Start formellt 1992. Malmö med i planeringsfasen. Umeå tecknade 1991 en överenskommelse med IARC om samarbete, formellt medlemskap 1996 (Malmö)1997 (Umeå). Intensiv vetenskaplig verksamhet. EU projekt, BBMRI- LPC tillsammans med BBMRI.eu. Samordning mellan Malmö och Umeå ang. etikansökningar, juridiska frågor kopplat till deltagande m.m. Svenskt förslag till utvidgat samarbete samt regelverk för ”sällansjukdomar”. CVD-projekt som f.n. vidareutvecklas med ett stort uttag av prover. DNA från 52 446. 67 Ett 30 tal forskare har varit engagerade från olika delar av Sverige och Finland. En pågående verksamhet där forskargrupperna samlats hösten 2012 i Spanien för ett BBMRI Nordic Heidelberg Göran Hallmans, Eva Lundin och Kjell Grankvist, Umeå. Helja-Marja Surcel, Oulu. I övrigt universitet i Tampere, finska folkhälsoinstitutet, finska cancer och födelseregistren. av alla gravida i Finland, f.n. 1.7 millioner prover från >90 0000 kvinnor. The Northern Sweden Maternity Cohort (NSMC) startades 1975. 150 000 prover från 100 000 kvinnor. Specifika valideringsstudier genomförda av serumkvalitet. PI:s enskilda projekt: 27 000 prover identifierade. Forskningen skall bedrivas på ett urval. Sverige: Göteborg Umeå Yvonne Wetter- Stockholm gren, Finland: Jörn Schneede, Helsingfors Joakim Dillner, Danmark: Lauri Aaltonen, Köpen-hamn Tine Jess, Norge Christer WingrenIsland Marie-Louise Färöarna Hammarström Estland Sten Hammarström Christina Hall Koordinator, Sverige: Johanna Ekström Övergripande 68 tre dagars möte. Inom infrastrukturen som är tveklöst världsledande inom området har ett antal valideringsstudier gjorts av de kliniskt insamlade materialen samt många bra vetenskapliga studier i övrigt. Genom det nedlagda arbetet har vi fått en god bild över användbarheten av maternitetskohorterna, som nu nyttjas inom en mängd andra studier inom ramen för detta BBMRI-program. Pilotstudier pågår över kartläggning av en genomisk signatur i bröstvävnad för genomgången graviditet. Publikation finns över prel. resultat. Fortsatt utveckling under 2014. Avsikten är att jämföra med signatur i blodprover. Etisk ansökan godkänd i Sverige och skrivandet pågår i Finland, Danmark och Norge. Arbete med registeransökningar pågår. Arbete med ansökningar till biobanker för uttag av DNA pågår. PI: Joakim Dillner Breast and Prostate Cancer Cohort Consortium (BPC3) Kontaktperson,Sverige : Mattias Johansson Umeå Ca. 10 000 fall kontroll material med DNA tillgängligt och analyserat. Projektet har pågått i många år med koordinering från NCI. BPC3 är ett av de mest produktiva konsortier som skapats under de sista 10 åren för att bl.a. studera genmiljöinteraktioner där prospektivt insamlade material är nödvändiga att ha. Aktiviteten relativt låg från svensk sida f.n. Mattias Johansson representerar Sverige i konsortiet. Lung Cancer Cohort Consortium (LC3) Mattias Johansson Umeå Ca 5 500 fall kontroll par med DNA, plasma/serum med speciellt focus på 1800 par av icke rökare. LC3 koordineras från bl.a. Umeå för att utvärdera faktorer som inte är relaterade till rökning för uppkomst av lungcancer. 20 deltagande kohorter. Finansiering från NCI med olika subproject finansierade från andra källor, bl.a. Cancerfonden. Kidney cancer cohort consortium (KIDRISK), Kontaktpersoner, Sverige: Börje Ljungberg Mattias Johansson Malin Sund Weimin Ye Umeå 10 000 fall kontroll par med DNA. KIDRISK genomför genetiska analyser och det leds av NCI tillsammans med IARC/WHO.. Umeå, Stockholm. 3851 fall, 3934 kontroller i PanScan. Det finns ett s.k. ”undantagstillstånd” via Datainspektionen efter långvariga förhandlingar. PanScan Pancreascancer EPIC 135 fall från Umeå Head and Neck Cancer Cohort Consortium (HNC3); ”HPV infektion Kontaktpersoner, Sverige: Umeå, Malmö/ Lund, Köpenhamn, 650 fall, 1 600 kontroller för serologi. Tumörmaterial insamlas för 69 DNA-prover och baselinedata finns distribuerat i projektet. Fortsatt analysarbete med flera publikationer klara. HNC3 har bildats för att utvärdera prediktorer för HPV orsakade tumörer i huvud-hals regionen. För Umeå och Malmö innebär detta att en och huvudhalscancer” Mattias Johansson, Johanna Ekström, EPIC, Lyon direktanalyser. Ca 100 tumörer Sverige/Norden (ca 80 från Sverige och 180 från Danmark) organisation etablerats inom Wp2 för att genomföra projektet som ett pilotprojekt med samtidig insamling av tumörvävnad. I denna process har gruppen som arbetat med detta stött på en hel del problem som dokumenterats. Serologiska analyser är redan utförda. Tumörmaterialen från Sverige är utplockade och analysering pågår. Det största materialet i sitt slag internationellt. Det första projektet av en rad projekt. Umeå, Malmö DNA extraheras från Umeå och analyseras av NCI GWAS chip. Information lämnas från Malmö när deras deras GWAS analys är klar? Totalmaterial planerat: Sekvenserade eller imputerade 10 558 fall och 11 812 kontroller. Planerad omfattning är 700 fall från Umeå. Ett omfattande planeringsarbete pågår mot bl.a. Datainspektionen (DI) för att få ett undantag beviljat med avsikt att data skall läggas på en avidentifierad hemsida inom NCI. Pressdebatt pågår om denna hemsida i USA och Sverige f.n. Danmark: Anne Tjønneland CRC : Genome-wide GeneEnvironment Interactions in CRC risk in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) Kontaktpersoner, Sverige: Ovarian Cancer Cohort Consortium Ovarian screening and risk markers Glioma Scan Anne Katrin LukanovaMcGregor, Eva Lundin, Annika Idahl. Umeå, Malmö, EPIC. Beatrice Melin, NCI, Umeå, Ingrid Ljuslinder, Jonas Manjer. Diskussionerna med DI har angående flertalet konsortieprojekt varit mycket tidskrävande och pågår fortfarande. Tidig diagnos av cancer kombinerat med studier över etiologi och patogenes. Projekt under uppbyggnad. 1 856 fall 4 955 kontroller; Bl.a. 14 kohort- 70 Pågående. The Metabolic Syndrome and Cancer Risk (Me-Can) CardioGram+ http://www.well.o x.ac.uk/mar-11genetic-links-tocoronary-heartdisease MAGIC (MetaAnalyses of Glucose and Insulin-related traits Consortium) http://www.magic investigators.org Plötslig Hjärtdöd CHARGE SCD (sudden cardiac death) Alicia Wolk, NCI medarbetare m.fl. Pär Stattin, Tanja Stocks, Jonas Manjer. Stockholm. studier. Umeå, Malmö, Köpenhamn. 578 700 individer, 289 866 män och 288 834 kvinnor. Paul Franks m.fl. svenska forskare. Från Sverige DNA från 140 : GLACIER - 000 individer, > studien samt 50 000 med CHD. olika kohorter. Paul Franks m fl. Från Sverige : ULSAM och GLACIER Paul Franks, Jan-Håkan Jansson, Stefan Escher, Olle Mellander Malmö /Lund, Umeå, Stockholm. Pågående. Me-Can som består av sju prospektiva kohorter från Sverige (Umeå och Malmö), Norge och Österrike. Pågående. Finansiering från WRC (World Cancer Research Fund). Pågående. Pågående. 472 fall från Medicinska biobanken + 1000 kontroller. Används för replikationsanalyser inom CHARGE SCD + 1148 + 118 fall med vävnadsprover från vilka DNA kan extraheras. I ett pilotprojekt har DNA extra-herats från 20 paraffinklotsar. 71 1. Pågående. Egna kohortstudier: Replikationskohort; Genealogier på 121 fall, familjestudier. DNA-prover finns distribuerade för exomanalys. För att expandera DNAmaterialet finns pilot genomförd på histopatologiskt material. 2. Internationellt konsortium där Sverige har en ledande ställning Första vetenskapliga projekten på gång inom kohorterna GIANT The Genetic Investigation of Anthropometric Traits http://www.broadi nstitute.org/collab oration/giant/inde x.php/GIANT_co nsortium GLGC: Global Lipids Genetics Consortium GEFOS/GENO MOS (Genetiska studier av Osteoporos/ frakturer) Dmitry Shungin, Paul Franks. Umeå, Malmö/ Lund. Kompletteras senare. Pågående. Hittills har det mycket stora gemensamma genetiska varianters om är förknippade med antropometriska egenskaper. Paul Franks Lund, Umeå. GWAS meta-analysis data från >100,000 individer för indentifikation av “lipid- and lipoprotein traits” Pågående. Sverige har en central roll via Paul Franks. Umeå, Göteborg, Malmö, Uppsala. 6 200 individer från Umeå samt 3 000 män totalt från övriga orter Aktiv forskning. Ett tjugotalmanuskript publicerade. Sverige har en central roll via Claes Ohlsson. Även andra svenska forskare deltar. Ulrika Pettersson Kymmer, Claes Ohlsson, Magnus Karlsson, Östen Ljunggren Metodstudier/valideringsstudier/återanvändning på/för/av biobanksmaterial Projekt PI/forskare Orter Antal prover, motsvarande Valideringsstudier alkylresorcinol Uppföljande studier på diabetes, colorectal cancer- Rikard Landberg, Marju OrhoMelander, Anne Tjønneland, Rob van Dam. Uppsala, Köpenhamn, Umeå, Malmö/Lund Harvard. Utveckling av ny metod, validering klar. 72 Status 2014-01 Metoden testas nationellt samt inom EPIC, Helga, Harvard m.m. De första publikationerna finns på plats, bl.a. inom EPIC: Plasma Alkylresorcinols, Biomarkers of Whole-Grain Wheat and Rye Intake, and Incidence of Colorectal Cancer Cecilie Kyrø, Anja Olsen, Biomarker discovery and validation (BioDiVa) Rikard Landberg, Alicia Wolk, Ingvar Bergdahl. Uppsala, Stockholm Umeå. 500 prover, plasma. Metabolomics analys i Uppsala. Uppföljning fettvävsbiopsier GWAS (Organisation och återanvändning) Ulrika Pettersson Kymmer, Åsa Torinsson Nalua Umeå, Stockholm Twingene: 12 600 Identifikation av en stabil folat degradationsprodukt Jörn Schneede, Per Ueland, Stephanie Scarmo. Bergen, Umeå, NewYork. Pilotstudie på serum från maternitetskohorten i Umeå. Metodstudier metabiolomics: Stabilitet av metaboliter vid långtidsförvaring i biobank Metodstudier långtidsförvaring av serumprover Linus Malm, Thomas Moritz, WP4 Umeå 110 prover, GC MS Calle Bengtsson, Cecilia Björkelund, Lauren Lissner, Göteborg Två omgångar serumprover, 26 resp. 29. Jämförelse GWAS-material i Umeå för återanvändning: ca 6 000 (9 olika material) 73 Rikard Landberg, et al. J Natl Cancer Inst; 2014;106:1–9 Uttag har beviljats i Umeå. Identifiering av individer och vilka prover som ska tas ut håller på att slutföras. Validering av en pågående EPIC-studie. Avsikten är dels att identifiera nya biomarkörer för kostintag, dels att studera måltidsmönster. Projekt i kontinuerligt operativ fas. Återanvändning pågår redan av regionala material i Umeå i minst 6 andra nationella/internationella GWAS-projekt. Fortsatt registrering av återanvändning. Kontinuerlig inkludering av fler nationella material. Slutsatsen av studien är att folsyra och folatnivåer kan skattas bl.a. via stabila degradationsprodukter i maternitetskohorterna. Av betydelse för en rad planerade projekt där diskussioner f.n. pågår. Pågående studie på olika material inom BBMRI.se. Prel. resultat redovisade och manuskript på gång. Kvinnostudien är en klassisk populationsbaserad studie med lång uppföljningstid som på detta sätt undersöks Kvinnostudien i Göteborg Tore Hällström, Margareta Ahlqwist, Ingmar Skoog, Göran Rybo. och Elisabeth Tibblin Rybo baseline 1968 med 2012. Undersökning av buffy coat lagrad i biobanker Ingvar Bergdahl tillsammans med en holländsk forskargrupp inom EUprojekt. Anders Johansson Forskare från olika länder inom ramen för ett EUprojekt. Umeå och Lund deltagit. Experimentella infrysningar och tinings- processer respektive infrusna och långtidslagrade prover från EPIC Italien och Umeå. Metodstudie: Performance in omics analyses of blood samples in long-term storage Dennie G.A.J Hebels, Ingvar Bergdahl, Göran Hallmans m fl. Maastricht Universitet, Nederländerna i samarbete med forskare vid Umeå universitet m fl. Utvecklande av nya metoder, speciellt trancriptomics metodologiskt. Resultaten finns i manuskriptform. Flertalet analyter tycks vara mätbara på ett bra sätt om relativa värden nyttjas. Tydliga intorkningseffekter samt protein degradationseffekter. Bl.a. RNA är mätbart på ett reproducerbart och användbart sätt. Standardiserad nedfrysning inom 2 timmar viktigt liksom metoden för upptining av prover. Lagringstid mindre viktig. Prel. metodstudier pågår av enskilda cellslag. 2 publikationer redovisade. Kan öppna helt nya möjligheter till genetiska studier. Metoden publicerad. Tillämpad på ett lymfommaterial som är accepterat för publikation. Lunds univ. har deltagit i planering av det övergripande projektet: EnviroGenomarkersmetodstudier om omics Uppbyggnad av nya kohorter samt uppgradering av gamla 74 Projekt PI/forskare Orter Antal individer Status 2014-01 HELGA kohorten Rikard Landberg, Lena Nilsson, Guri Skeie, Anja Olsen, Anne Tjønneland. Uppsala, Umeå, Tromsö, Köpenhamn 120 000 Samordning EPIC Danmark, Norge och Umeå. Färdiguppbyggd 2012 med inkludering av kliniska data, projekt påbörjade. Oklart om behov finns av BBMRI- stöd. Komplettering med kliniska data. POL Näspolyp/astmastudie Mats Bende Christel Larsson, Göteborg, Skövde 700 Kvinnostudien i Göteborg Cecilia Björkelund, Lauren Lissner Göteborg 1462 insamlade 1968 - 2010 Psoriasis, celiaki och tidiga biomarkörer Marcus SchmittEgenolÅsa Torinsson Naluai Göteborg, Umeå 1500 (fall + familjer i Gbg) + ca 1500 fall i Umeå Pågående. Målet äratt samla inminst1000patienter inkl släktingar med denna sjukdom och att studera bakgrunden till denna kroniska inflammatoriska sjukdom och dess relation till astma. Pågående. Uppföljning av en epidemiologisk studie tillägnad kvinnors hälsa som startade redan 1968. Områden av intresse är (fetma,demens, klimakteriet,östrogenbehandlin g, sömn störningar) . Metodstudier sker även ang. provers kvalitet, se metodstudier ovan. I planeringsfas. GLACIER Paul Franks med medarbetare från ett flertal Medarbetare över hela landet och internationell - diabetes.. Många studier har utförts och publicerats. Många projekt pågår och många fler planeras. 75 - diabetes exom - epigenetik sjukdomsområden t i olika konstellationer Osteoarthritis Ulrika Pettersson Kymmer, Claes Ohlsson Torsten Johansson Henrik Grönberg Umeå , Göteborg, Edinburgh, Rotterdam, Linköping Kari Hemminki Forskare i Malmö och Umeå. Mikrobiotaprojekt Mikael Johansson, Mattias Johansson Ingegerd Johansson, Skall samordnas med NIMB, se nedan. Anne Tanner, Forsyth (Harvard affiliering). Caps studien Prostatcancer Genetik vid cancersjukdom av oklart ursprung;” Genome-wide association study on CUP (Cancer of unknown primary site)” Tidig diagnos av Lungcancer 4 400 fall av OA som genomgått plastik har identifierats i medicinska biobanken, Umeå Ca 10 000 prover och 5 000 individer Wareham N Malmö, Umeå, Heidelberg, EPIC. 400 fall i Malmö och Umeå. Cancer av okänt ursprung utgör 3-5 % av alla cancer men eftersom det rör sig om en nästan alltid dödlig sjukdom så utgör gruppen den fjärde största angående död i cancer. Etikansökan beviljad. GWAS material från UFO studien återanvänds Umeå, Valideringsstudie i Malmö. Umeå 400 + 400 fall Pågående, finansierad av Cancerfonden. 3000 faeces-, saliv- och munbiofilm prover från spädoch småbarn Microarray- eller s.k. next generation sekvenseringar av DNA extraherat från biofilmer, faeces eller sekret, dels indirekt genom Den ekologiska balansen i tarm och munhåla, har relaterats till att fler sjukdomstillstånd som fetma och allergi, kardio-metabola sjukdomar. Stockholm , Umeå. Replikering 500 fall i EPIC och 500 fall i Tyskland 76 Capsstudien. Prostatcancer. antikroppstitrar. Utveckling av infrastrukturer för specifika behov för myndigheter, inkl sjukvård och industri. Projekt PI/forskare Orter Engagerade myndigheter, Status 2014-01 Företag m.m. Nationell Humanbiologisk Miljöprovbank (NHMB) Ingvar Bergdahl, Nationell styrgrupp från Stockholm, Lund. Uppsala, Umeå. Hela Sverige. Högt deltagande i MONICA studien medför att proverna verkligen är representativa för befolkningen. Detta gäller även maternitetskohorterna som är användbara för vissa specifika syften. 77 Naturvårdsverket, Livsmedelsverket, Socialstyrelsen, Folkhälsomyndigheten, Kemikalieinspektionen. Finansiering från Naturvårdsverket samt stödbrev från Livsmedelsverket Under vidareutveckling. En viktig komponent i detta är MONICA-projektet med prover tagna på ett populationsbaserat material ca var 5:e år sedan 1986, men genom att via WP2 engagera miljömedicinska forskare och kliniker runtom i Sverige skulle biobanker kunna nyttjas bättre för att få underlag för bedömningar av miljöhälsorisker. Den 7:e MONICA-undersökningen genomförs våren 2014 och dess miljödel har planerats inom NHMB, där Naturvårdsverket, Livsmedelsverket, Kemikalieinspektionen, Folkhälsomyndigheten (tidigare Socialstyrelsen) och Läkemedelsverket, liksom Lunds och Göteborgs universitet samt KI/Institutet för miljömedicin, har varit med. Nationell immunitets och mikrobiologisk biobank (NIMB) Anders Johansson, Björn Olsen, Anders Sjöstedt m.fl. Hela Sverige Umeå, Uppsala f.n. SMI/Folkhälsomy ndigheten, FOI Under uppstart efter planeringsfas. NIMB har utvecklats ur NHMB där immunitetskomponenten och den mikrobiella komponenten funnits med under ett antal år. Ett forskningsprogram är nu klart som underlag för finansiering. Infrastrukturer för genetisk rådgivning Behandlande läkare vid olika kliniker. Samtliga kohorter; populationsbaserade. Kontinuerlig verksamhet för spridning till övriga landet. Registrering av antal tillfällen och var biobanker nyttjas. Industriellt, prekompetetivt Alzheimerprojekt Intresseförfrågan från företag via EPIC Umeå, Inventering planeras i övriga landet inom WP2. Umeå klart Malmö funderar Företaget är initiativtagare men anges inte här. Ligger i linje med det koncept som skisserats av David Cox Flera överläggningar har ägt rum i olika former. Idén är att internationellt kraftsamla för att skapa system för tidig diagnos av Alzheimer, vilket öppnar nya terapeutiska fönster. Nya viktiga resultat inom Umeå kohorterna som pekar mot en möjlig virusetiologi. http://vimeo.com/ 9052672 Utveckling av nya register som kopplas till biobanker Projekt PI/Forskare Orter Antal fall med prover 78 Status 2014-01 Alzheimer Sture Eriksson, Kaj Blennov m.fl. Nationellt 400 validerade, betydligt fler registerbaserade. Biobankskohort definierad och godkänd för analys. 380 validerade fall. Nationellt under uppbyggnad. Start Västerbotten. Medel söks för koppling nationellt till befintliga biobanker. Parkinson Lars Forsgren, Jesper Pettersson Umeå, Malmö/Lund Ventrombos Nationellt projekt Lars Johansson, Jan-Håkan Jansson, Anders Själander, Peter Svensson Umeå, Malmö/Lund, Sundsvall, Mellan 2006 och 2011 har ca 900 prospektiva fall inkluderats i VäV Nationell (Västerbottens inbjudan avses ventrombossändas ut när tiden är inne för register) projektlansering. Totalantal beräknade fall: 2 300. I norra Sverige är förutsättningarna unika för att bedriva forskning om riskmarkörer tack vare Västerbottens hälsoundersökningar (VHU) och den Medicinska Biobanken,(MB) som utgör en förutsättning för Västerbottens ventrombosregister (VäV). Klaffsjukdoms studie Stefan Söderberg Koordineras från Umeå. 2 000 DNAprover. Digitalisering av barnhälsovårdsjournaler i Väster- Sven-Arne Silverdal Pilotprojekt för användning i den nationella vaccinationsövervakningen Samordning med serumbiobanker kopplade till den nationella immunitets- 79 Nationellt under uppbyggnad Databasen i VÄV är samordnad med ventrombosregistret i Malmö. Registeruppbyggnad klar avseende delmål. Ev. fortsättning. Studie definierad avseende DNA, extraktion pågår. Plasma- och enkätstudie planeras för 2013. Nationell inbjudan ska gå ut för deltagande i studiens forskningsdel när infrastrukturen nu är uppbyggd. Landstingsstöd + ansökningar om fortsatt finansiering pågår. Uppgifter på tillväxt och vaccinationer i en databas som ett led i kartläggning av biobanken botten långtidseffekter av vaccinationer. Kommentar om världsledande sammantagna infrastrukturer för bröst- och prostataforskning: Sverige har en klart världsledande ställning beträffande infrastrukturer och forskning om prostatacancer och bröstcancer. Materialen utgörs dels av olika nationella biobanksmaterial, dels av en kraftfull utveckling av Nationella Prostatacancerregistret (NPCR)/ databasen PCBase som samkörs med andra nationella register såsom Patientregistret, Flergenerationsregistret, Dödsorsaksregistret och Läkemedelsregistret. Den världsledande ställningen kring internationell biobanksforskning bekräftas både av publikationer och erhållna internationella anslag. Det ligger inom WP2:s ansvarsområde att hantera denna samordning på ett konstruktivt sätt inom bl.a. ramen för BBMRI.se:s regelverk. Ekonomisk redovisning inklusive vilka andra betydande bidrag som har sökts/fåtts: - NorthPop-organisation: Ansökan Wallenberg Nationella humanbiologiska miljöprovbanken: Anslag från Naturvårdsverket för specifika insatser. Stödbrev från Livsmedelsverket. BBMRI Nordic, Nordforsk - Paul Franks, Lund: - Gene-Lifestyle Interactions in Dental Endpoints (GLIDE). Vetenskapsrådet, 20122015 (PIs: Johansson/Franks, Umeå/Lund, Sweden) The G-FORCE Study: The Genetics of a Fatal Outcome Resulting from a Cardiac Event Study. Svenska Hjärt- och Lungfonden. 2013-2015 (PI: P Franks The VIKING Study: The Västerbotten Imputation databank of Near-complete Genomes - a stratified medicines initiative for genetically complex diseases.Vetenskapsrådet, 2013-2016 (PI: P Franks, Umeå/Lund, Sweden) - Rikard Landberg Uppsala (HELGA- kohorten samt biomarkörutveckling för biobanksforskning): - Strategiska forskningsmedel från SLU (2013-2014), anslag från FORMAS (20122014), VR (2012-2014), samt Styrelsen för forskning och innovation, Danmark (2012-2016 PI: Anja Olsen). Hans Lilja Malmö/Lund och Pär Stattin, Umeå för bearbetning av infrastrukturen för prostatcancerstudier från de kombinerade Malmö- och Umeå kohorterna: - Nuvarande stöd: 80 NCI/NIH (R33 CA 127768-03) PI: Lilja. Phased innovation research in cancer prognosis and prediction (R33). Project Title: Long-term prediction of prostate cancer death from kallikreins measured in blood. - Förväntat stöd: NCI/NIH (R01 CA175491-01) PI: Klein. Project title: “Improving prostate cancer screening by integration of SNPs with blood biomarkers.” Inskickad publication NEJM. Ali Moazzami (Assistant Professor), SLU Uppsala: - SciLifeLab, metabolome wide association study on prostate cancer has been approved. Prover har levererats under 2013. 81
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