Nordic Biobank Collaboration –

Opportunities and Obstacles Joakim Dillner

Director, BBMRI.se (Sweden)

Johanna Ekström Coordinator for BBMRI Nordic pilot project in Sweden

What are the Nordic advantages, really?

-Possibility to link biobanks to

nationwide, comprehensive registries on health data, heredity and

sociodemographic factors

Personal Identification Number (PIN)

Health care Registries Biobanks

Registry infrastructure in the Nordic countries

•A unique number given at birth or at immigration

•Collect health data for e.g. cancer and birth data.

•It is mandatory to report health events to nationwide registers

•Health care

•Research

•The registries use the PIN •The health

care system uses the PIN

•The biobanks use the PIN

Biobanks with follow-up – an essential infrastructure for medical

research • Biobanking roots: samples and baseline data

• Follow-up for disease and cause of death

Biobanking is not just about not having to collect samples – it is about not having to wait for the outcomes

Strategic development of biobank and registry resources

→a unique Nordic advantage

Biobanks with follow-up – an essential infrastructure for medical

research • Etiological research

-Causal exposures may have occurred long ago

• Prevention research -Future diagnoses must be known

Exposure Disease

Sample occasion

BIOBANK STUDY BASE

Registry/ies 1. Application 2. Selection of case & controls 3. Case verification 4. Data retrieval 5. Validation of data quality

Biobank/s 1. Application 2. Selection of case & controls 3. Case verification 4. Sample & data retrieval 5. Validation of sample & data

quality

Scientific coordination: The user perspective

Scientists (PIs) with idea of how to use samples & data

BBMRI Nordic coordinators assist with performing registry linkages and sample/data retrieval

If assembled data and samples are found to be sufficiently comparable and of high quality –>

analysis can start

2-4 yrs

Scientific coordination: The biobank perspective

→ Biobank

• Limited scientific impact by multiple small projects

• Questionable scientific validity – different hypotheses can not be compared unless included in the same study

• Limited scientific impact of non-coordinated studies threatens the long-term sustainability of the biobanks

Scientific coordination: The scientific perspective

• Research on etiology -all risk factors should be studied

→Exactly the same study base with samples and data should be used

• Predictive sciences -all biomarkers and predictive

factors should be studied

→Exactly the same study base with samples and data should be used

BBMRI Nordic (Nordic Biobank Network) NordForsk-funded Collaborative Network between the National Biobanking

Infrastructures in the Nordic Countries

• Identify and validate samples and data

• Study bases built for one disease at a time -clinical data and data on exposures -samples taken both before, at and after diagnosis

Generation and exploitation of Nordic Biobank materials for medical research

• Combine genealogy, prospective cohorts and exposure assessments in several generations

• Use the best available and useful expertise and technologies to fulfill the best possible research purposes applied on the study bases

Generation and exploitation of Nordic Biobank materials for medical research

BBMRI Nordic Pilot

• Colon cancer selected as pilot disease

• Expected Result: Very large-scale Nordic study providing information from registries and biobanks, on the etiology and early diagnosis of a pilot disease

• If successful, concept could be copied to enable joint Nordic studies on any disease

The BBMRI Nordic pilot project on joint biobank-based research

• Is a research project - it is not a new biobank

• The national biobank platforms will:

-Systematically identify i) cases and controls and ii) accessory data from Nordic biobanks using registry linkages using PINs

-File applications for ethical permission & biobank withdrawals

• This ”ready-to-use” infrastructure will then be made openly available to Nordic scientists

The BBMRI Nordic pilot project on joint biobank-based research

• A real-life standardisation & harmonisation project in the Nordic countries

• High –profile project: to show that the Nordic countries can indeed collaborate on biobank- based sciences • Optimises the scientific output from biobanks

by facilitation of more large-scale sciences

Schematic overview of the study Aim

Cancer registry Statistic Sweden

Environmental, clinical & sample data

Biobanks Sample retrieval

Nordic PI’s

Heredity in the Nordic countries

Effect of environmental exposure

Validation papers on methods, screening & verification

Possible biomarkers for early discovery and best possible treatment

Relations

CRC cases

Biobanks

Research project

Genotyping of Colorectal cancer risk SNPs Principal Investigator: Lauri Aaltonen, Professor

Department of Medical Genetics, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland

Genotyping the known >20 CRC risk SNPs in sufficient number of cases and controls should shed light on possible additive effects of risk genotypes and exposure.

Ethical application - piloted by Sweden

• Very general in concept: ”A joint Nordic study on etiology and diagnosis of colorectal cancer.”

-Genomics, proteomics, transcriptomics, metabolomics…

-Waiving of consent applied for

-Biobanks to use: All biobanks registered at the Swedish National Board of Health and Welfare

-Ethical and legal arguments checked by BBMRI.se ethicists and lawyers

Ethical application Response from Ethical Review board: • Be more specific on the analyses. • Waiving of consent approved, but include a communication plan

for conveying information to the public via media, internet and patient organisations

Action by BBMRI Nordic: • Updated the Ethical application with specifics on analyses and

included a ambitious communication plan Result: • Ethical application approved Conclusion: • The permission has established that large-scale, joint Nordic

biobank-based research is allowed also with the present ethical/legal framework.

Some identified bottlenecks

• No clear legal basis for general and infrastructural projects – only for ”specific” projects

-Solution: Collection of specific projects added to the Nordic work plan already from the start. Caused significant delays

• Some scientific experts say no to collaboration

• The Open Access principle was not as widely accepted as we thought

Some identified bottlenecks

• Different ways of working for the biobanks

-withdrawals are independent with each hypothesis separated from others, even on the same disease

-other biobanks are more disease-oriented with a coordinating scientist for each disease

Disease-orientation instead of Project-orientation?

• Biobank in the center • Research data on disease archived at the

biobank -Enables investigating effect of confounding

• No legal obstacles for large-scale data (except that interlinkage requires new permission).

Nordic biobanks as key players for international research

• If we ensure that collaborating Nordic biobank cohorts are similarly followed-up for disease endpoints et c using registry linkages – we will create a uniquely large and uniquely reliable study base for molecular research

Opportunities for Nordic biobank collaboration

• Routine linkages of biobanks to registries has important implications on development of best practises – notably on how to handle personal identfiers

• It is mostly the Nordic countries who fully understand this issue – crucial to participate in the European development in this area

Summary

• Formalities were laborious – but BBMRI Nordic has established that large-scale, joint Nordic biobank-based research

-on all biobanks in a country

-for quite broad hypotheses

is possible and allowed also with the present ethical/legal framework

Summary

• Issues within the scientific community very important

-Genuine will to share both data and samples (Open Access)

-Similar way of working required (preferably disease-oriented with continuous adding of new data to the biobank cohorts)

-Genuine will to collaborate outside the home university

Acknowledgements

• BBMRI Nordic is funded by NordForsk

• Johanna Ekström & Joakim Dillner (S); Tine Jess, Jan Wohlfahrt & Mads Melbye (DK); Eivind Ness-Jensen & Kristian Hveem (N); Miia Artama, Eero Pukkala & Anu Jalanko (FIN); Andres Metspalu (EE); Jon G Jonasson (IS); Gudrid Andorsdottir (Faeroese)

• Very large number of biobank managers and interested scientists in all the Nordic countries