Medicel (AOECS 2011) PATIENT FIRST – AT THE CENTER BIOBANKING

1. Medicel (AOECS 2011) PATIENT FIRST – AT THE CENTERBIOBANKING Thomas M Attard MD FAAP FACG Associate Professor of Pediatrics, Physiology The University of Malta Medical School Consultant Pediatrician, Gastroenterologist Mater Dei Hospital, B’Kara, Malta

2. What is a Biobank? “A collection of biological material and the associated data and information stored in an organised system, for a population or a large subset of a population.” Organisation for Economic Co-operation and Development (OECD)

3. Why do we need a Biobank? • Medicel→ consortium of pediatric gastroenterologists from Mediterranean & Surrounding Countries • Represented countries face challenges re. unique population, diversity of cultures and evolving resources • Way ahead includes studying our unique population • A biobank through integration of molecular data with the clinical information represents a single, organized, common resource that can be utilized to perform multiple hypothesis-driven studies, interface with industry and monitor the evolution of CD in our societies

4. Advantages of a Biobank • Statistical Power • Large number of samples collected over years but available instantly • Cost • Reduces costs, as once collected the collections remains available for a number of studies • Harmonised standard operating procedures and best practice yields a more efficient and time-saving collection of samples which are quality assured • Logistics • greater potential for translational research projects and will facilitate clinical trials. • development of centralised IT infrastructure creates access for many more users -incentive to collaborate. • Ethics • Single ethical approval and well controlled ethical processes – lessens the time in setting up the individual biobank as well as strengthens client trust

5. Population • Two large groups of Biobanks • Whole population • Subset of population • Whole population • Collection of samples from a large number of the general population • Not disease specific • Useful for epidemiological studies as well as prospective studies • Subset of population • Collections from a subset of the population with specific conditions • Includes family collections • Useful to identify the causes (both genetic and environmental) of the condition • This is the type that is most of interest to our group

6. Biological Material • Any biological material can form part of a biobank • Most common include: • Fixed tissue samples • similar to the pathological biobanks present in most of the World’s hospitals. • tissue is usually derived from pathologically altered tissue and is usually fixed. • advent of new molecular biology techniques and the ability to isolate single cells from the fixed tissue, both abnormal and normal DNA as well as RNA information is available. • information on the protein structure is severely limited and it is not possible to obtain living and thus reproducing cells from the fixed tissues. • DNA/RNA banks • genetic material (DNA or RNA), usually isolated from white blood cells, or from other donor tissue. • stored either as deep-frozen (DNA or RNA) or as dry samples (DNA) for a relatively long period of time.

7. Biological Material (Cont’d) • Body Fluids • Storage of body fluids (plasma, serum, cerebrospinal fluid, urine) usually at very low freezing temperature (< -80oC) • Useful to identify fluid composition at a point in time • Cell culture banks • Consists of donor samples (usually blood cells but could also be any other living, nucleated cells) are transformed into permanent cell cultures. • They are usually stored in very low freezing temperature (usually under liquid nitrogen) and thus, at least theoretically, constitute an inexhaustible source of DNA of almost unlimited durability. • They can also be utilised to study gene function, expression and cellular functions.

8. Organisation of Samples and Data • Samples need to be organised in a way that they can be easily identified and withdrawn from bank • Use of well designed storage area • Organisation of data • Standardised design • Electronic database • Control on data accesibility

9. Population Patient Personal TISSUE DATA Demographic Clinical Biobank research product Organization – Storage Retrieval Analysis

10. Multisite Organized BIOBANK(s) INFORMATION Biologic material -TISSUE • Storage: • Local • National • Regional • Central Identifier Demographic Clinical PRIVATE / (local) primary investigator CONSORTIUM PUBLIC Consortium protocol samples Investigator / institutional samples • ANALYTICAL INFRASTRUCTURE: • Advanced methods of tissue analysis • IT support • Coordinate research • Interface with Industry

11. Requirements for a Successful Biobank Infrastructure - Blood

12. Requirements for a Successful Biobank Infrastructure - Living Tissues

13. Requirements for a Successful Biobank • Information Technology • Adequate database containing the fullest data possible • Adequate security measures in place to safeguard data protection • Easy protocols to share data between researchers • Adequate measures to identify ownership as well as recognition • Laboratory facilities • Medium level – sample preparation • High Level – for advanced analysis

14. European Initiatives • Various local/national biobanks • Need to harmonise • Best setup: • Actual biobank situated at local level • Centralised (with mirroring and backing) IT infrastructure available through a web based interface • Regional advanced laboratory facilities • This was identified by the EU - setup of BBMRI

15. BBMRI - Biobanking and Biomolecular Resources Research Infrastructure • Funded by EC through ERIC (European Research Infrastructure Consortium) legal entity. • 53-member consortium with over 280 associated organisations (largely biobanks) from over 30 countries - largest research infrastructure project in Europe. • will form interface between specimens and data and top-level biological and medical research. • achieved through a distributed research infrastructure with operational units in all participating Member States.

16. BBMRI Participants

17. Ethical Considerations Informed consent of the donor • a universally acceptable principle. • implies that the person has the “capacity to give consent.” • “capacity to give consent” • to understand the purposes, nature, significance and implications of the measure calling for consent, • believe that information; • to weigh the pros and cons and • to exercise the right of self-determination in the light of the understanding arrived at.

18. Ethical Considerations - Consent • Types of Consent: • ‘Blanket’ consent • Limited Consent: • Consent to recruit into biobank • Consent for particular study • Consent for future studies • Consent for particular types of future study egs. Genetic / lab – diagnostic / academic vs. industry • Consent to be contacted re. future studies • Default accept / decline participation?

19. Ethical Considerations Data Protection • Ability to trace back the identity the donor can be an issue where the samples are not anonymized • various methods by which the data can be coded: • Direct identification • Coded - identifiable data is physically separated from the personal data but the procurer of the sample has access to the code • Encrypted - third party persons transform the code into a number of characters, thus identificable by third party • Anonymized - connection between the code and the identifiable data is completely lost • Anonymous - samples were donated in a completely anonymous form → no personal identifier data

20. Ethical Considerations Secondary Use of Stored Tissues • ability to use the tissues for a research not anticipated for when the tissues were originally harvested. • Ideally all research on archival material should have had prior consent for that study, in actual fact in most cases not available and not feasible to obtain . • As yet no consensual agreement on this ethical issue – range from very rigid approach - no studies can be undertaken on archival material unless with prior consent to more flexible approach where the decision based on • the traceability or otherwise of the person, • the possible anticipated use as compared to the original use, • the risk implications of the research on the individual and • the type of consent at the time of collection. • A common thread is that there is a need for an approval from an independent committee.

21. Ethical Considerations: Commercialisation of stored biological tissue and Remuneration • EU Member States adhere to the principle that donations of human tissues must be free, • only compensation to cover travel expenses and loss of earnings. • In general information generated from studies on donated tissues belongs to the researcher or team that creates it and that the individual who may have been a subject of the research has no legal entitlements to that research - but by far this view is not universal.

22. Ethical Considerations:Genetic discrimination and stigmatisation Genetic discrimination • Person’s genetic background resulting in unequal treatment • particularly so when applied to employment and insurance contracts. • This risk is increased where large volumes of data are assembled, as in biobanks. • addressed by adequate legislation as well as ethical guidelines. Genetic stigmatisation • Stigmatisation is a problem of perception by others or self – difficult to legislate on. • Carrier individuals might be classified - stigmatisation • impact on the donor’s relatives of any identification of genetic disease. Donor is protected by proper consent guidelines, relatives and even entire groups of people, who have no previous knowledge of the genetic disease, might find themselves the recipient of this information and may not wish to possess it.

23. Conclusion • Biobanks are useful to as a research tool • Reduce the time and expense of research • Should be set up in a collaborative way were infrastructure is shared • Requires robust legal and ethical regulations which • Idea of regional hubs should be encouraged

24. Acknowledgements: • Prof. Chris Scerri Univ. of Malta • AOECS 2011