Cancer in the context of Biobanks ' Societal issues: ethics, law and public dialogue

1
Cancer in the context of Biobanks .Societal
issues ethics, law and public dialogue

• Anne Cambon-Thomsen,
• Directrice de recherche au CNRS
• Inserm U 558, Epidémiologie et analyses en
  santé publique, Toulouse, France
• Ancien Membre du CCNE,
• membre GEE (Groupe européen déthique)

Cambon-Thomsen, Nat Rev Genet, 2004, 5,
866-873. Rial-Sebbag, Médecine/Sciences, 2006,
vol 22.. 8-14
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A multidisciplinary team on Genomics, health and
society
Equipe Génomique, santé, société Inserm U
558 Epidémiologie et analyses en santé
publique Faculté de médecine, 37 allées Jules
Guesde, Toulouse
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http//genopole-toulouse.prd.fr/
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Present experiences allow this platform to
address the following objectives

• Bring support to members of genomic research
  community using platform facilities to better
  identify and address the societal issues in their
  activities (cycles of thematic seminars,
  educational sessions, documentation etc.)
• Organize the response to demands of interactions
  from various publics
• Assist institutional partners in their genomics
  societal impact analyses (follow up and reports
  on specific subjects)
• Bring an adequate support for the axes Genetics,
  science and society aspects of EU and other
  international projects
• Contact Anne Cambon Thomsen, cambon_at_cict.fr
• http//genopole-toulouse.prd.fr/layout.php?pageho
  me2id186langfr

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Biobanks Questions of sources, of evolving
uses, of societal views on an activity...

• What are the issues?
• What are the rules?
• Who sets the rules?
• How to proceed in practice?

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Context and Definition (s)
Uses of samples and/or uses of data. Medical
(diagnostic, follow up, therapeutic), research,
development and quality control. Limits not
always clear between the different uses.
Biobanks the biological samples themselves,
plus the related databases, allowing a certain
level of accessibility, availability and exchange
for scientific studies.
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Actors and their context
Commercial Interests
Ethical principles Legal regulation
Scientist(s)
Donors
Medical Applications
Patients associations Media RECs (IRBs)
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The variety of biobanks
The issues extend beyond genetic testing The
context of their constitution/use is
variable They constitute key tools for research
and development in genetic testing Large
biobanks are developing, but many smaller exist
and are useful.
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Whats at stake?

• the rapid pace of change has produced two
  powerful, but conflicting, social reactions. On
  the one hand, there is very strong public support
  for breakthroughs promising better medical
  diagnosis and treatments on the other, there
  are anxieties about increased loss of privacy and
  the potential for genetic discrimination, as well
  as about the capacity to regulate genetic science
  in the public interest.
• Essentially Yours The Protection of Human
  Genetic Information in Australia, Australian Law
  Reform Commission, 2003.

Biobanks are not only for genetic uses but
genetic and genomics are developed more and more
and can always appear even with samples not
collected initially with this aim.
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Ethical issues and points of tension underlined
Development of research Developments over the
years unclear Commercial biobanks Easy access
to them without complications Rights of
priority of researchers / companies
Rights of persons / groups Correct information
prior consent / old banks Non commercial use of
human body parts Quality of sample conservation/
management Optimal transparent use of samples
data
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The status Persons, Samples and Data

• Part of the human body
• Information about the person
• Information about the family
• Information about a group of individuals
  (population)
• All rules and recommendations tend to pull in one
  of these two directions
• Part of a person
• Information about a person or a group
• New concept sample considered as information
  carrier (CDBI)
• When does a sample become a product?
• When does a sample become data?

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Ethical framework in France

• Besides the legal rules there are
• guidelines of good practices (http//www.oriamnet
  .com/Databiotec/databiotec_content.htm Chart)
• And
• opinions of the National French Advisory
  Bioethics Committee (http//www.ccne-ethique.fr/en
  glish/start.htm
• Opinions 25 (1991), 60 (1999), 77 (2003)

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French National Bioethics Committee views on
biobanking, 2003

• Complexity of the legal framework in France that
  (over)regulates in practice biobanking activities
  in different contexts and does not give so far a
  clear unified status to collections (this has
  been taken into account in the revision of
  bioethics laws)
• Absence of status of the professional biobankers
• Difficulty and the limits of the repeated
  informed consent in the case of long term use
• Necessity of a somewhat extended consent, but
  with extensive information on the foreseen
  activities
• Consequent need of stronger security and
  protection of individual information

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French National Bioethics Committee views on
biobanking, 2003

• Suitability of a contact body for people to
  follow and get information on what is being done,
  over time
• Balance to be found between the rights of
  researchers who have set up collections, on
  their future use and the openess for optimal
  exploitation may vary according to situations
  but must be clarified
• Notion that, besides the individual rights, there
  appears a new form of solidarity between groups
  and between generations, based on the volunteer
  sharing of samples and information for a common
  good this opens to large population biobanks

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French National Bioethics Committee views on
biobanking, 2003

• necessary clarification of the public and/or
  private frame of biobanking and the corresponding
  guidelines, the present situation being too
  foggy
• necessity for the public power to handle the
  question of regulation of biobanks in order to
  make possible to tackle with clarity the legal,
  economical and international exchange policies
  instead of the present jungle
• the CCNE insists on the importance to fix some
  limits on the envisaged activities, even with a
  larger consent
• no blank consent that looses its meaning

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French National Bioethics Committee views on
biobanking, 2003

• it reminds of the non commercialisation and non
  availability of elements of the human body
• thus, no proprietary right of persons
• absolute frontier between scientific/medical use
  and judiciary/police use
• it affirms the necessity and responsibility of
  the public institutions to regulate this activity
  in a realistic way and to set up regulating
  bodies able to organise the control of this
  activity, especially in the context of large
  national biobanks
• large biobanks needs to be democratically
  discussed

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Specific questions

• Is there a unified ethical framework in Europe?
• Is large scale population biobanking modifying
  the picture for all biobanks?
• Is ethics promoting or preventing sharing of
  bioresources and data?

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The report 25 Recommendations of the EC Expert
Group on the Ethical, Legal and Social
Implications of Genetic TestingConference on
Human genetic testing what implications?
Brussels, May 6-7, 2004
http//europa.eu.int/comm/research/conferences/200
4/genetic/index_en.html 
Comment at http//www.ircm.qc.ca/bioethique/obsge
netique/
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R3 genetic exceptionalismR20 Existing and new
biobanks.R 21 Collections of human biological
material and associated data and their useR23
Informed consentR24 Samples from the
deceasedR25 Consent for children and vulnerable
individuals

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Recommendations

• Guidelines across the EU to ensure proper use of
  samples
• Member states ensure a competent review committee
  to be consulted before research
• Inventory of existing biobanks and their
  characteristics
• Implement a system to monitor and evaluate their
  usage
• EU following closely activities along this side
  in Member States and the global context
• Contact with OECD Biological Resource Centres
  task force
• EU take initiative in co-ordination with other
  ongoing activities regarding regulatory issues
  related to collections of human biological
  material and associated data and their use in
  research

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What sort of regulations?

• Specific law?
• Existing laws clarification for their
  application to biobanks specificities?
• Recommendations?
• All models exist
• Leave a part to projects themselves with
  appropriate supervision
• Review in Cambon-Thomsen et al.
  http//www.humgen.umontreal.ca/int/GE.cfm

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Practical application of an ethical framework
Informed consent more or less large External
committee Data protection Rules of
access Relevance of the degree of identification
of the individual sample donor/ right to withdraw
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Different practical situations (1)Source of
samples /data

• Use of existing samples /data Be careful!
• obtained in situations of health care (tissues,
  sera, cells)
• obtained in situations of donation (blood,
  sperm)
• obtained in the context of a research project
• Constitution of a new collection of samples and
  data Think ahead!

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Different practical situations (2)Characteristics
of samples/data

• Degree of possible identification of persons
  through samples
• Identifying
• Traceable or identifiable or coded
• Anonymised
• Anonymous

• Type of persons concerned
• Families or non related individuals
• Adult or minor or other situations
• Healthy or disease affected person

Scientific validity (?) Re-consent
Committee Scientific validity
Committee Scientific validity /- Committee
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Semantic Interoperability

• Knoppers BM, Saginur M. The Babel of genetic data
  terminology. Nat Biotechnol 200523(8)925-7

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DIRECTIVE OF THE EUROPEAN PARLIAMENT AND OF THE
COUNCIL (2004/23/EC)
http//europa.eu.int/comm/health/ph_threats/human_
substance/legal_tissues_cells_en.htm

• Scope
• Setting standards for quality and safety for
  donation, procurement, testing, processing,
  preservation, storage and distribution of human
  tissues and cells intended for human application
• All types of cells/tissues are covered, incl.
  HSC, cord blood, bone marrow, foetal
  cell/tissues, embryonic stem cells
• Excluded in vitro research, tissues, organs and
  cells used for transplantation and for direct
  autologous grafts, blood and blood products
  (directives 2001/83/EC, 2000/70/EC, Council
  Recommendation 98/463/EC, 2002/98/EC))

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European Ethical Guidelines
European Commission Research Directorate-General
Survey on opinions from National Ethics
Committees or similar bodies, Public debates and
national legislation in relation to human
biobanks
Directorate E-Life Sciences Biotechnology,
agriculture and food research Edited by Line
Matthiessen Line-Gertrud.Matthiessen-Guyader_at_cec.e
u.int Last revision October 2004
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• Ongoing debates on
• Informed consent (ind., group, enlarged..)
• Right to receive feed-back information
• Conditions for opting-out/withdraw
• Use of anonymised specimens
• Protection of personal data (is DNA data?)
• Selling and buying tissues

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International collaboration

• The full benefits for which the subjects gave
  their samples will be realized through maximizing
  collaborative high quality research. Therefore
  there is an ethical imperative to promote access
  and exchange of information.
• Data Storage and DNA Banking for Biomedical
  Research Technical, Social and Ethical Issues,
  ESHG, 2001, art. 17.

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International harmonization

• the changing conditions of genetic research
  call for the establishment of an international
  instrument that would enable States to agree on
  ethical principles, which they would then have to
  transpose into their legislation.
• Report of the Secretary-General on information
  and comments received from Governments and
  relevant international organizations and
  functional commissions pursuant to Council
  resolution 2001/39 (11)

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National ethics committees, European group of
ethics (EGE), Council of Europe (CDBI), UNESCO
Int Bioethics Committee (IBC), WHO

• Several national ethics committees have or are
  currently preparing an opinion related to
  biobanking (France 2003, N 77 Germany 2004,
  Switzerland, 2005)
• EGE
• opinion 11 in 1998 on tissue banking
• opinion 19 in 2004 on Cord blood banking
• CDBI of Council of Europe recommendations about
  Human sample use in research (2005)
• The IBC (UNESCO) adopted in Oct 2003, an
  International Declaration on Human Genetic
  Databases (including samples)
• WHO working on a set of recommendations (brain
  storming 2006)

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International initiatives towards harmonization

• BRC (biological resource centre, OECD)
• European FP6 Concerted Action POPULATION BIOBANK
  (18 partners, Coordination Public Health
  Institute, Oslo) From March 2006 (C Stoltenberg)
• P3G Public population project in genomics
  (Canada, BM Knoppers)

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Specific questions

• Is there a unified ethical framework in Europe?
• Is large scale population biobanking modifying
  the picture?
• Is ethics promoting or preventing sharing of
  bioresources and data?

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In the context of genomics large population
biobanks biobank-omics
Ref CAMBON-THOMSEN A et al. 2003, Comparative
functional genomics, 4  628-634 LObservatoire
de la génétique, 2003, N10 http//www.ircm.qc.ca/
bioethique/obsgenetique

• Scale is changing (Ex Iceland, Estonia, Sweden,
  UK)
• Size
• Time
• Uses
• Throughput
• Are we facing biobank-omics?
• Has this change in scale and scope impact on
  ethical issues and their handling?

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The UK Biobank Project
Aims to recruit 500 000 individuals aged 45-69 on
a voluntary basis trough general practitioners
throughout UK Physical assessment, personal
history, lifestyle questionnaire, blood
sample Details on illness, cause of death
obtained through NHS medical records long-term
follow-up National database Run by Medical
Research Council and Wellcome Trust Budget
100 M
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Towards Biobank-omics
Donors interests views
Population genetics Genetic epidemiology Genes
involved in disease process Pharmacogenetics Pharm
acogenomics
Organs, cells, DNA
transplant
products
regeneration
DNA-sequences

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When working at population level Public
consultation

• Respecting the principles of reciprocity and
  accountability requires that research on a given
  population be based upon open dialogue between
  the population and the research team(s). A
  guiding mechanism for population genetic research
  is prior and ongoing public consultation.
• Statement of Principles on the Ethical Conduct of
  Human Genetic Research Involving Populations,
  RMGA, Jan 2003, art. 1.

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Ethical dimensions are challenged by
 biobank-omics 

• The scale of studies pushes towards
• less individualism and new solidarity, balanced
  with more protection of data
• Besides the individual rights, there appears a
  new form of solidarity between groups and between
  generations, based on the volunteer sharing of
  samples and information, for a common good
• large biobanks precious national resource for
  whom?
• more democratic debate and management

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Actors and their context
Commercial Interests
Ethical principles Legal regulation
Population debate, information bodies
Scientists
Donors
Medical Applications
Information Cooperation Integrity
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The tendencies

• Large consent, double coded
• Possibility of follow up of what is being done
  with samples, data
• Withdrawal (limits, samples, data)
• More sophisticated data security technical tool
• Empowerment of research ethics committee
• Specification of what will be done after death
• Information, communication (cancer area of
  considerable interest from the public)

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In conclusion

• Human genetics/genomics and cancer biobanks
  obliged fields!
• Ethical issues in biobanking do matter for
  international activities, although ethics remain
  a national competency
• Ethics is different from legal obligations
• A number of web resources available for
  national/international texts
• Informed consent is not a magical tool and should
  be considered as a factor of dialogue, not only a
  legal or formal obligation
• Importance to follow up with the changes of
  social attitudes in considering issues and the
  appearance of new regulations
• Responsibility of researchers and their
  organisations
• For clarifying the issues /transparency
• For education
• For position/recommendation
• For keeping relevant authorities aware
• For stimulation of debate and dialogue

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Thanks for your attention!
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Useful references of web sites

• Council of Europe Convention dOviedo
• http//www.coe.int/T/E/Legal_Affairs/Legal_co-ope
  ration/Bioethics/Texts_and_documents/1Treaties_COE
  .aspTopOfPage
• Other international texts or access to texts
• http//europa.eu.int/comm/research/science-society
  /ethics/legislation_en.html
• ASHG www.faseb.org/genetics/ashg/policy/pol-25.h
  tm
• UNESCO www.unesco.org/ibc/fr/genome/projet/index
  .html
• WHO http//www.who.int/genomics/elsi/resources/e
  n/
• HUGO www.gene.ucl.ac.uk/hugo/conduct.htm
  /sampling.html
• HGDP ww.stanford.edu/group/morrinst/hgdp/protoco
  l/html
• National Bioethics Advisory Commission
  www.nih.gov/index.html The use of human
  biological materials in research Ethical issues
  and policy guidance
• OECD report on Biological Resource Centers
  http//www.oecd.org/
• ESHG www.eshg.org (EuroGapp)
• Canadian site Humgen http//www.humgen.umontreal
  .ca
• Guidelines, model consent and population genetics
  declaration of principles at www.rmga.qc.ca
  (Réseau de médecine génétique appliquée)

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Publications by members of A. Cambon-Thomsen team
on informed consent biobanks ethical/legal/socia
l issues (2000 2004)

• Assessing the impact of biobanks CAMBON-THOMSEN
  A, Nat Genet, 2003, 34, (1) 25 - 26
• An empirical survey on biobanking of human
  genetic material and data in six EU countries.
  HIRTZLIN I. et al., Eur J Hum Genet, 2003,
  11475-488
• Biobanks for genomics and genomics for biobanks.
  CAMBON-THOMSEN A., DUCOURNAU P., GOURRAUD P.A.,
  PONTILLE D. 2003, Comparative and functional
  genomics, 4  628-634
• The social and ethical issues of post-genomic
  biobanks. CAMBON-THOMSEN A., Nature Reviews
  Genetics, 2004, 5, 866-873
• DNA donor's viewpoint on the consent device.
  DUCOURNAU P., New Genetics and Society, (accepted
  2004)
• DUGUET AM, THOMAS A RIAL E, DUCHIER J,
  CAMBON-THOMSEN A., Rev. Médecine légale droit
  médical, 2000, 43, N7.8, 637-641
• CAMBON-THOMSEN A., Rev. Haut Comité de la Santé
  Publique, 2001, 34, 55-61
• DUBREUIL C., DUCHIER J., CAMBON-THOMSEN A. Rev.
  Prat, 2001, 51, 469-472
• CAMBON-THOMSEN A., Rev. Epidemiol. Santé
  Publique. 2003, 51 99.
• CAMBON-THOMSEN A,. RIAL-SEBBAG E., Rev.
  Epidemiol. Santé Publique. 2003, 51  101-110.
• RIAL-SEBBAG E., Rev. Epidemiol. Santé Publique.
  2003, 51 111-120 .
• CAMBON-THOMSEN A. RIAL-SEBBAG E. DUCHIER J., Rev.
  Epidemiol. Santé Pub. 2003, 51 121-26.
• CAMBON-THOMSEN A LObservatoire de la génétique,
  2003, NAvril 2003, 2004 Mars, Août , Novembre
  2004 http//www.ircm.qc.ca/bioethique/obsgenetiqu
  e/
• CAMBON-THOMSEN A Les cahiers du Comité
  Consultatif National dEthique, 2004, 38 39-42
  et 2004, N de Nov. 2004
• DUCOURNAU P. Sciences Sociales et Santé, in press
  2005