1. business and industrial
2. business operations
3. business plans

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.
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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
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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
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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
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BBMRI.se Service Centers
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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
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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.
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B. Basic Infrastructure (= continuous improvement of continuous service)
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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)
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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:
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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.
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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.
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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
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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
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Charter with principles and template for informed consent, through a web-based version
called Consent Shaper.
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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
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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:
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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
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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.
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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,
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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/).
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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.
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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)
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
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
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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.
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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
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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:
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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.
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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.
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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.
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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
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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
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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