Ethical aspects of biobanks and progress status of the Genome Project in Latvia

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Ethical aspects of biobanks and progress status
of the Genome Project in Latvia

• Valdis Pirags
• Seminar for the Research Ethics Committees of the
  Baltic countries
• Skolas iela 3, Riga
• May 9-10, 2008

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Background

• Biomedical research utilising stored human
  biological materials is a powerful tool to
  improve human health and healthcare systems
• The primary intention of research undertaken on
  human biological materials is to advance
  knowledge so that patients in general may benefit
  

Recommendation on research on human biological
materials, Council of Europe, 2005
3
Controversybiomedical research vs medical
practice
In biomedical research the primary intention is
to advance knowledge so that patients in general
may benefit
In medical practice the sole intention is to
benefit the individual patient
Knowledge of general benefit may emerge from the
clinical experience gained
An individual research participant may or may not
benefit directly
Convention on Human Rights and Biomedicine, on
Biomedical Research, draft additional Protocol,
2003
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Ethical problem

• How to make knowledge of general benefit gained
  from the biomedical research useful for every
  individual patient?

Solution
Population based health and genome databases
Risks
Social or psychological risks to the gene donors
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1.Introduction to the population based Genome
Projects
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Development and transformation of the Latvian
Genome Project

1. Initiative group for the human genome research in
   Latvia created (1999). First proposal of the
   Latvian Genome Project submitted to the
   government
2. Collaboration programme Genetic Studies of
   Latvian Population, Application for Diagnosis and
   Prevention of Human Pathology funded by the
   Latvian Council of Science (since 2001)
3. Pilot project Genome Database of the Latvian
   Population funded directly by the government
   (2003)
4. National Research Programme Study of the main
   pathologies threatening the life expectancy and
   quality of the Latvian population supervised by
   the Ministry of Education and Science (2006-2009)

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Collaboration project funded by the Latvian
Science Council Latvijas populacijas genofonda
izpete saistiba ar cilveka patologiju

• Research on genetic factors regulating metabolism
  and homeostasis (Janis Klovinš)
• Molecular Genetics of the Coronary Heart Disease
  (Normunds Licis)
• The role of pharmacogenetics in treatment of
  oncologic diseases (Aija Line)
• The influence of genetic factors on development
  of hereditary breast and ovary cancer (Laima
  Tihomirova)
• Molecular genetic charasteristics of the Latvian
  population (Viesturs Baumanis)
• Diagnostics of mutations influencing the
  pathogenesis of monogenic diseases (Inta
  Vasiljeva)
• Elaboration of molecular genetic methods and
  their use in genetic research Services of the
  Latvian Genome Centre (Elmars Grens)

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Genome Database of the Latvian Population the
main project

• November 1, 2006. The Cabinet of Ministers
  authorized the Latvian Biomedical Research and
  Study Centre to create the Genome Database of the
  Latvian Population.
• March 22, 2007. The Central Medical Ethics
  Committee approved the protocols and documents
  used by the Genome Database of the Latvian
  Population
• September 20, 2007. The Latvian Genome Centre
  started to collect the samples and data in
  collaboration with the general practitioners and
  largest hospitals

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Latvian Genome Database Recruitment Update 5,732
(May 2008)
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National Research Programme in Medicine
(2006-2009)

• Multidisciplinary research consortium on the main
  pathologies threatening the life expectancy and
  the quality of life of the Latvian Population
• The recruitment target for the years 2008-2009 is
  4,000 randomly selected and carefully phenotyped
  individuals from all parts of Latvia

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Proposed population biobank projects in Europe
2000-2006
Goals 1.Understand the interaction between
genes, environment, lifestyle and
disease 2.Create the engine for the transfer of
this knowledge to health care systems
DeCODE Genetics in Iceland
EGP in Estonia
LGP in Latvia
UK Biobank in UK
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Promoting Harmonisation of Epidemiological
Biobanks in Europe (PHOEBE) 6FP (2007-8)
The Norwegian Institute of Public Health
(coordinator)
National Public Health Institute, Finland
Karolinska Institutet, Sweden
Aim a collaborative research network that will
identify and explore key issues that will help to
ensure that Europe makes best use of its rich
array of population-based biobanks and
longitudinal cohort studies
McGill University, Canada
UK Biobank
University of Tartu, Estonia
University of Leicester, UK
Charles University, Czech Rep.
University of Bristol, UK
Imperial College of Science, Technology and
Medicine, UK
INSERM U558, France
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Genome banks and networks in Europe (2008)

• Public Health Genomics (PHGEN)http//www.phgen.nr
  w.de/typo3/index.php
• The German National Genome Research
  Networkhttp//www.ngfn.de/englisch/index.htm
• UK Biobankhttp//www.ukbiobank.ac.uk/
• Molecular Phenotyping to Accelerate Genomic
  EpidemiologyMolPAGEhttp//molpage.org/pubs.asp
• European Network of Genomic and Genetic
  Epidemiology (ENGAGE)http//www.euengage.org/scie
  nce.html

• Biobanks for health in Norwayhttp//www.fhi.no/ew
  ay/default0.asp?e0pid225
• Genome Database of the Latvian Population
• http//biomed.lu.lv/gene/
• Estonian Genome Project Foundationhttp//www.geen
  ivaramu.ee/index.php?langengshowmain
• GenomeEUtwinhttp//www.genomeutwin.org/
• Public Population Projects in Genomics
  (P3G)http//www.p3gconsortium.org/
• P3G Observatoryhttp//www.p3gobservatory.org

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Public Population Projects in Genomics (P3G)
Membersare international, national or regional
not-for-profit organizations that are conducting,
or will be conducting a large population genomics
project such as a biobank or a large-scale cohort
study (Ngt10 000 samples)

• ALSPAC (UK)CARTaGENE (Canada)Centre for
  Integrated Genomic Medical Research (United
  Kingdom)Danubian Biobank Foundation
  (Germany)Estonian Genome Project
  (Estonia)Generation Scotland (UK)GenomEUtwin
  (Finland)INMEGEN (Mexico)INSERM (France)King
  Saud bin Abdulaziz, University for Health
  Sciences (Saudi Arabia)KORA-gen
  (Germany)LifeGene (Sweden)

• LifeLines Cohort (Netherlands) National Cancer
  Institute (USA)National Heart, Lung and Blood
  Institute (USA)Norwegian Institute of Public
  Health (Norway)NUgene Project (USA)Ontario
  Cohort Consortium (Canada)Singapore Tissue
  Network (Singapore)Taiwan Biobank Institute of
  Biomedical Sciences, Academia Sinica (Taiwan)UK
  BioBank (UK)Western Australian Genome Health
  Project (Australia)

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UK Biobank Recruitment Update 114,217 (9pm
Thursday 8 May 2008)

• UK Biobank is a major UK medical research
  initiative, and a registered charity in its own
  right, with the aim of improving the prevention,
  diagnosis and treatment of a wide range of
  serious and life-threatening illnesses
  including
• cancer,
• heart diseases,
• diabetes,
• arthritis
• forms of dementia
• UK Biobank is now recruiting 500,000 people aged
  40-69 from across the country to take part in
  this project
• UK Biobank Ethics and Governance Council

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Estonian Genome Project Recruitment Update
18,141 (May 2008)
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Legislation specific to Biobanks

• Act on Biobanks , Iceland/Government, Ministry of
  Health and Social Security (Iceland, 2000).
• Government regulation on a Health Sector Database
  , Iceland/Government - Ministry of Health and
  Social Security (Iceland, 2000).
• Human Genes Research Act , Estonia/Government
  (Estonia, 2000).
• Human Genome Research Law , Latvia/Government
  (Latvia, 2002).
• Act Relating to Biobanks , Norway/Government
  (Norway, 2003).
• Biobanks in Medical Care Act , Sweden/Government
  (Sweden, 2003).
• Human Tissue Act 2004 , United Kingdom/Government
  (United Kingdom, 2004).

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Selected guidelines and reports

• Australian Law Reform Commission (2003)
  Essentially Yours The Protection of Human
  Genetic Information in Australia - contains 144
  recommandations of the commission
• WHO's European Partnership on Patients' Rights
  and Citizens' Empowerment (2004) Genetic
  databases assessing the benefits and the impact
  on human and patient rights - the ethical,
  social and legal issues that surround the
  creation and operation of databases containing
  human genetic material
• Fonds de la recherche en santé du Québec (2006)
  Governance Framework for Data Banks and Biobanks
  Used for Health Research the final report by
  the Advisory Group on the collection, processing,
  utilization, storage and management of data banks
  and biobanks for health research purposes
• the Bioethics Advisory Committee, Singapore
  (2007) Personal Information in Biomedical
  Research - a report discussing the need to use
  personal information in biomedical research and
  makes recommendations aimed at establishing
  principles for data protection and confidentiality

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Comparison of Latvian and Estonian Genome projects
Latvian Genome Project Estonian Genome Project
Main aim To create a national system of genomic and health information storage and data processing To establish a Gene Bank, that contains health and genetic data on the people of Estonia
Legal basis The Human Genes Research Act passed by parliament in June 2002, amended in June 2003 The Human Genes Research Act passed by parliament in December 2000
Owner-ship The genome database is operated by the state scientific institution authorized by the government and controlled by the Council of Genome Database The gene bank belongs to the Estonian Genome Project Foundation
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Initial comparison of Latvian and Estonian Genome
projects 2006
Latvian Genome Project (similarities to the UK Biobank) Estonian Genome Project (similarities to the DeCODE Genetics)
Funding The establishment of the genome database is funded by the government The establishment of the Gene Bank is funded by investors and funds
Profit Main processor of the genome database may not have profit from utilization of coded tissue samples, DNA descriptions and health descriptions Founders of the Gene Bank may have profit from scientific and applied discoveries
Coding and decoding Coding is performed by the main processor under supervision of the State Data Inspection. Decoding is performed by the State Population Genome Register Coding and decoding can be performed by the EGPF only under supervision of the Data Protection Inspectorate
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2. Ethical aspects of population biobanks-
what is the best way of data protection?-
ownership of biological materials and data
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Long tradition of data collection Latvian
Folklore Repository has more than 1 500 000
entries, circa 400 000 folk songs, including 4
000 naughty dainas
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More than 5 000 DNA samples and associated data
(including potentially sensitive data) are filed
in the Latvian Genome Data Base in 2008
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Contains diagnosis completed according to the
International Classification of Diseases.
Information is based on documentation in medical
records
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Contains 45 questions including information on
ethnicity, life stile, family, anthropometry,
disease status (more detailed on cancer,
cardiovascular and endocrine diseases)
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No. 34,343received fromR.Berzinšliving
inDžukste
Identified data in the Latvian Folklore
Repository
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Identifiability of biological materials and
associated data

• Biological materials and associated data should
  be anonymised as far as appropriate to the
  research activities concerned.
• Identifiable materials and data should not be
  utilised if there are less intrusive means to
  reach similar results.
• Where there are identifiers, it is necessary to
  have a well-developed framework of protections to
  ensure that the risks to sources of human
  biological materials and data are minimised.
• However, it must be kept in mind that in some
  cases, unlinked anonymisation might not be
  appropriate in the interests of the persons
  concerned or for scientific reasons.

Recommendation on research on human biological
materials, Council of Europe, 2005
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Identifiability of biological materials and
associated data

• Any use of biological materials and associated
  data in an identified, coded, or linked
  anonymised form should be justified by the
  researcher
• Ethics committees should ask researchers
  proposing to use unlinked anonymised biological
  materials to justify this choice in terms of the
  inevitable consequence that it means that there
  will be no possibility of giving health-related
  feedback resulting from the research to persons
  concerned

Recommendation on research on human biological
materials, Council of Europe, 2005
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Organisation for Economic Cooperation and
Development
DRAFT GUIDELINES FOR HUMAN BIOBANKS AND GENETIC
RESEARCH DATABASES 2008
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The aim of the Guidelines

• to provide guidance on the establishment,
  governance, management and use of Human Biobanks
  and Genetic Research Databases (HBGRDs) used for
  purposes of genetic research.

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1. HBGRDs Generally

• The objective of a HBGRD should be to foster
  research within legal norms and ethical
  principles.
• ...
• The HBGRD should consider and minimise risks to
  individuals, their families and potentially
  identifiable populations or groups whose
  specimens and data are included in the HBGRD and
  used for research.

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2. Establishment of HBGRDs

• The purpose(s), both current and future, of the
  HBGRD should be clearly formulated, and
  communicated as early and as widely as possible,
  especially to potential participants and
  potential users.
• In the establishment of the HBGRD, the initiators
  should carry out consultations with stakeholders
  and the general public.
• The HBGRD should develop a business plan,
  including a financial model, that it intends to
  adopt over its lifespan in order to ensure its
  sustainability.
• The HBGRD should be explicit and transparent
  about the nature and source of its
  financing/funding.

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3. Governance, Management, and Oversight

• The HBGRD should be governed by the principles of
  transparency and accountability.
• The initiators of the HBGRD should clearly
  formulate the governance structure and management
  responsibilities applicable to the HBGRD and
  should make available information to
  participants, stakeholders and the general
  public.
• The governance structure should ensure that the
  rights and well-being of the participant prevail
  over the research interests of the initiators and
  users of the HBGRD.
• Within its governance structure, the HBGRD should
  have a mechanism to review applications for
  access to the human biological materials and/or
  data

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4. Terms of Participation

• HBGRDs should obtain prior, free and informed
  consent from each participant. Where applicable,
  HBGRDs should provide for obtaining consent or
  authorisation from the appropriate substitute
  decision-maker.
• HBGRDs should give careful consideration to any
  special issues related to the participation of
  vulnerable populations or groups, including
  children, individuals with impaired
  decision-making capacity, and prisoners.
• During the informed consent process, HBGRDs
  should provide potential participants with
  sufficient information on the nature,
  implications, foreseeable risks and benefits of
  their participation, so that they can
  realistically assess the implications of their
  participation and can make an informed decision
  on whether to participate. This information
  should be presented so as to not constitute an
  improper inducement to participate in the
  research.

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4. Terms of Participation

• HBGRDs should have a clearly articulated policy
  on the nature of the feedback that will be
  provided to participants, taking into account any
  domestic legal requirements. This policy should
  cover the feedback of individual-level results,
  if any, as well as aggregate results arising from
  research carried out using human biological
  materials and/or data from the HBGRD.
• Participants should be provided with the
  opportunity to decide on whether or not to
  receive feedback of individual-level results
  arising from research.
• As a general rule, non-validated results from
  scientific research using a HBGRDs human
  biological materials and data should not be
  reported back to the participants and this should
  be explained to participants during the consent
  process.
• Where a HBGRD has offered and the participant has
  elected to receive feedback of individual-level
  results, and depending on the nature of the
  feedback, it may be appropriate for a trained
  professional to provide this feedback to
  participants or for counselling to be available
  to participants.
• HBGRDs should have a clearly articulated policy
  on whether participants will be re-contacted
  during the course of the HBGRDs existence, the
  situations for which re-contact will be
  permitted, and the conditions that will govern
  re-contact.

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5. Contents of HBGRDs

• HBGRDs should have a clearly articulated policy
  and should communicate to potential participants
  which human biological materials and data will be
  collected from them or from other sources, stored
  and used for research purposes.
• HBGRDs should have a clearly articulated policy
  on whether data will be accessed from health or
  other records, independently assembled, and
  whether or not these data will be linked with or
  stored in the HBGRD. Such a policy should also
  address the issue of secondary use of health and
  other records, especially when combined with
  other data. Where HBGRDs intend to access data
  from health or other records, it should ensure
  that participants are duly informed and that
  their informed consent for accessing such records
  is obtained.

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6. Protection of Human Biological Materials and
Data

• HBGRDs should be established, managed and
  governed in such a way as to prevent any
  inappropriate or unauthorised uses of
  participants human biological materials and
  data.
• HBGRDs should establish policies and procedures
  for the protection of the human biological
  materials and data, especially those potentially
  permitting, whether directly or indirectly, the
  identification of the participant.
• The HBGRD should ensure that the data and
  information contained within its databases should
  be protected in accordance with applicable
  domestic law, especially in regard to the
  protection of privacy.

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7. Access

• HBGRDs should develop clear policies and
  procedures for accessing human biological
  materials and data in their databases, which
  should be based on objective and clearly
  articulated criteria.
• Access and use of human biological material and
  data should be consistent with the terms of
  participation and should respect the privacy of
  the participant and confidentiality of the human
  biological materials and data.
• HBGRDs should provide participants with explicit
  information on whether or not their human
  biological materials and data, in whole or in
  part, will be made accessible to third parties
  for non-research purposes.
• The HBGRD should not make accessible or disclose
  participants human biological materials or data
  obtained for health research purposes to third
  parties for non-research purposes, including to
  insurance providers, employers, or to law
  enforcement agencies, except where required by
  law. The informed consent document should be
  transparent and explicit about any legal
  requirements to share human biological materials
  or data with third parties.
• Unless strictly necessary, researchers should be
  provided access only to human biological
  materials, data or information that is coded such
  that the participant cannot be identified and
  researchers should be required to not attempt to
  re-identify participants. Such exceptional
  conditions should be clearly disclosed to
  research participants during the informed consent
  process.

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7. Access

• 7.F HBGRDs should have a clearly articulated
  policy on whether researchers using its
  database(s) will be allowed to contact
  participants directly.
• 7.G Given the potentially finite nature of human
  biological materials, HBGRDs should formulate
  criteria for prioritising applications for access
  to the human biological materials.
• 7.H The terms of access for researchers to the
  whole or a part of the database(s) of an HBGRD
  should be set out in an access agreement.
• 7.I Where a HBGRD intends to provide access to
  the specimens and samples collected from
  participants, they should develop a material
  transfer agreement or other agreement appropriate
  for that purpose.
• 7.J HBGRDs should only transfer specimens and
  data when there are adequate standards in place
  regarding privacy of the participant and
  confidentiality of the data, safety and good
  laboratory methods and in accordance with
  applicable law and regulations.

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8. Qualification, Education and Training

• The HBGRD should ensure that all of its personnel
  are knowledgeable about its goals and mission.
• The managing person(s) of the HBGRD should be
  qualified by training and experience to carry out
  its mandate.
• The managing person of the HBGRD should ensure
  that personnel have the appropriate professional
  qualifications that meet recognised standards,
  underpinned by experience, education and training
  and are assigned responsibilities commensurate
  with their capabilities.
• The managing person(s) of the HBGRD should
  develop and implement employee training
  programmes.

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9. Custodianship, Benefit-sharing and
Intellectual Property

• HBGRDs should have a clearly articulated policy
  on whether participants retain any rights in the
  human biological materials and data, and the
  nature of these rights.
• Where the HBGRD intends to retain rights to the
  participants human biological materials and/or
  data, it should have a clearly articulated
  policy, which should be explicitly indicated to
  the participant and should be included in the
  consent document(s). Such policy should be
  consistent with applicable law, and regulatory
  and ethical best practices.
• Benefits arising from research using the HBGRDs
  resources should be shared as broadly as
  possible. Benefits may be shared in different
  ways including the sharing of information,
  licensing, or transferring of technology or
  materials.

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10. Demise of the HBGRD and Disposal of Materials
and Data

• The HBGRD should plan for an unforeseen demise,
  such as the end of its funding.
• The initiators of a HBGRD should consider a
  possible end date for this endeavour.
• In accordance with applicable law, a HBGRD should
  have a detailed policy setting out the manner in
  which the human biological materials and data
  that it holds will be dealt with in the event of
  its demise.
• Once a HBGRD is no longer required or is no
  longer of scientific value, the human biological
  materials and data should be disposed of in an
  appropriate way, consistent with the principles
  of consent and privacy.