Consent and confidentiality in population genetics and epidemiological research: Ethical aspects of biobanking in an international context Is ethics promoting or preventing sharing? Bartha Maria Knopppers Anne Cambon-Thomsen

1
Consent and confidentiality in population
genetics and epidemiological research Ethical
aspects of biobanking in an international
contextIs ethics promoting or preventing
sharing?Bartha Maria KnopppersAnne
Cambon-Thomsen
August 21, 2004
GenomEUtwin ethics educational meeting, Oslo
2
A.I Informed Consent The Framework

• Legal and Socio- Ethical Context
• With the assistance of Madelaine Saginur

3
Guiding principles

• Human dignity
• Human rights and fundamental freedoms
• Autonomy
• Privacy
• Non-discrimination and non-stigmatization

4
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.

5
Universal Declaration on the Human Genome and
Human Rights, UNESCO, 1997.

• Need to address ethical issues of genetics
  (preamble)
• Genome common heritage of humanity (art. 1)
• Respect individuals uniqueness and diversity
  (art. 2)
• Non-commodification of the human genome (art. 4)
• Benefit-sharing (art. 12)
• Freedom of research (art. 12)
• Solidarity (art. 17)
• International co-operation (arts. 18, 19)
• The Universal Declaration is a starting point it
  is now up to the States to put the Declaration
  into practice

6
International texts and guidelines

• Nuremberg Code (1947).
• Helsinki Declaration (1964 - 2002).
• Directives from WHO. (Manille, 1981-).
• Statements HUGO (1996 -).
• UNESCO Declaration (December 1997 - ).
• Convention of Council of Europe (Oviedo, 1997).
• Recommendations ESHG (2001 -).
• US texts (NBAC) in USA (1999)
• Declaration of principles for research in
  genetics and in population genetics (Quebec, 2000
  - 2002)
• French and German National ethics committees
  working in 2003-04 on a statement on biobanks

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A.I Informed Consent The Framework

• Examples from Europe

8
European Diversity
9
Irreducible Differences
Beer
Wine
10
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 February 2002, revised October 2002,
present revision under way, will be web
accessible
11
The 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 
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R20 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

13
Analysis of practices through consent forms used
in genetic research in France

• Obtaining a sample of consent forms and the
  attached information sheet used in genetic
  research (151 included in the study used before
  1998)
• Analysis of their content according to three
  views
• law
• research
• person being a research subject
• Comments and proposals

From de la Dorie, 1998 and Cambon-Thomsen de la
Dorie, 1999
14
Results the 9 criteria of the French law on
protection of biomedical research participants
15
Conclusion

• Consents
• Often do not completely fulfill the law
  requirements
• Some issues are poorly addressed outcome of
  sample, feed back of results, opinion of a minor,
  exchanges, non profit or for profit use
• Law requirements must not hide true ethical
  issues and do not prevent debates on sensitive
  issues
• There is an heterogeneity between research ethics
  committees even within one country
• When becoming objects of research human beings
  remain free subjects.

16
A.I Informed Consent The Framework

• Examples from North America

17
Historical position

• No individual, specific consent ? no research
• Yes individual, specific consent ? yes research
• Not accounted for
• - relevance of genetic data beyond the
  individual
• - effect on the family/community
• - public consultation? (a)
• - long-term relevance of genetic data
• - waiver of consent? (b)
• - broad/blanket consent? (c)
• - re-consent? (d)

18
Tri-Council Policy Statement Ethical Conduct
for Research Involving Humans, Canada, 1998

• Broadening possibilities of consent
• - provision of a number of options on consent
  form
• a) use of the material only in the present
  study
• b) use restricted to the condition or
• c) other clearly specified uses
• - specifying arrangements to maintain contact
  with the subject regarding future uses

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(a) Public consultation

• Needed to
• Achieve transparency
• Ensure acceptance of the project
• Address publics concerns
• Not consent per se however, strong opposition
  could jeopardize project
• Before and during commencement of the project

20
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. 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.

21
Public consultation

• research on identifiable community ? community
  consultation
• minimize harm for the community.
• substantial opposition within the community ?
  investigators should not conduct the study.
• support of community ? still obtain individual
  consent in the usual manner
• E-2.079 Safeguards in the Use of DNA Databanks in
  Genomic Research, American Medical Association,
  June 2002, art. (2).

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(b) Waiver of consent

• Consent requirements can be waived if
• the research involves no more than minimal risk
  to the subjects,
• the waiver will not adversely affect the rights
  and welfare of the subjects,
• the research could not practicably be carried out
  without the waiver, and
• whenever appropriate, the subjects will be
  provided with additional pertinent information
  after participation
• NBAC (1999) p.66 See also AMA (2003) TCPS
  (1998)

23
Relationship between level of identifiability of
data and waiver

• In NBACs judgment, where the research uses
  identified or coded samples from previously
  collected specimens, such uses usually are not
  justified without the sources consent, because
  the risks to sources and others may be more than
  minimal. However, the use of unidentified or
  unlinked samples for research could be justified
  in some cases if other appropriate protections
  were in place, despite the lack of informed
  consent.
• NBAC (1999) p.71

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(c) Broad/blanket consent

• When human biological materials are collected,
  whether in a research or clinical setting, it is
  appropriate to ask subjects for their consent to
  future use of their samples, even when such uses
  are at the time unknown.
• NBAC (1999) p.63

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(d) Re-consent

• Consent is a continuing process and must be
  reconfirmed for instance in the case of
  significant changes to the research protocol, to
  the conditions of banking
• RMGA (2003) art. 3.

26
Core elements of informed consent

• Prior consent
• Protection of privacy
• Duration of conservation
• Return of results
• Transfer, access
• Extension or future research
• Commercial issues
• Benefit sharing

• Written information
• Aim of the research
• Methodology
• Duration of research
• Risks/benefits
• Constraints
• Ethical committee
• Right to participate or not
• Right to withdraw

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Analysis of consent forms Results
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Towards convergence?

• Items of relevance
• Clarification of how those items are addressed in
  a given cultural context
• Work at multidisciplinary level to construct
  information packages and consent forms
• But, do not overestimate the written document
  interaction is important
• Consent as a process not a procedure
• Take advantage of current technology

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A.II Informed Consent The Process

• Communication by Researchers/Clinicians What, to
  whom, when?

30
A.II Informed Consent The Process

• Right to know
• Right not to know
• General vs. specific results
• If researcher does not know wishes of subject
• Danger of providing information
• Issues specifically applicable to biological
  relatives

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Return of results A balancing act

• Right to know
• Duty to warn this is the secret to make the
  bullets line up. You will soon be written in
  white. How sneaky!
• Biological relatives data potentially of medical
  interest to them

• Right not to know
• Danger of providing information that is very
  preliminary/ without counselling/ where no
  treatment available
• Biological relatives privacy of donor of genetic
  sample

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(a) Right to know

• No one should be denied access to his own
  genetic data
• UNESCO (2003) art. 13.
• Personally identifiable information should be
  subject to adequate subject access rights
• WHO (2003) rec. 18.
• after the completion of the study, subjects
  will be informed of the finding of the research
  in general, and individual subjects will be
  informed of any finding that relates to their
  particular health status
• CIOMS (2002) Guideline 5(7).

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Right not to know

• the person concerned has the right to
  decide whether or not to be informed of the
  results
• UNESCO (2003) art. 10.
• Adequate account must be taken of the privacy
  interest that individuals have in not knowing
  information about themselves.
• WHO (2003) rec. 16.

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(b) General vs. specificresults

• General
• Results should be made public
• It is reasonable to expect that researchers
  should communicate with the population and the
  relevant governmental authorities regarding
  results that are pertinent to the improvement of
  health and/or the prevention of disease
• RMGA (2003) 6.

35
(c) General vs. specificresults

• Specific
• Should the participant wish to be recontacted to
  obtain the results, he should remain in contact
  with the researcher in charge (i.e. updating of
  coordinates)
• Results should be communicated to the participant
  when
• they are scientifically valid,
• They have significant implications for the health
  of the participant, and
• prevention or treatment is available
• RMGA (2000) II.4, IV.3

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(d) If researcher does notknow wishes of subject

• in circumstances where there is no evidence
  of what an individual would want to know, it is
  not possible to ask them if they would wish to
  know, for to do so is to indicate that there is,
  indeed, something to know, and thereby any
  possible harm will have been caused.
• WHO (2003) section 5.3.

37
If researcher does notknow wishes of subject

• Before any unsolicited approach is made, the
  following factors must be considered
• The availability of a cure or therapy
• The severity of the condition and the likelihood
  of onset
• The nature of the genetic disease
• continued

38
If researcher does notknow wishes of subject

• The genetic nature of the disease, i.e. that it
  might have significant implications for blood
  relatives
• The nature of any genetic testing that will be
  required
• The question of how the individual might be
  affected if subjected to unwarranted information,
  and whether the individual has expressed any
  views on receiving information of this kind.
• WHO (2003) rec. 16

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(e) Danger of providing information

• outside of clinical setting
• not evaluated in context of the full medical
  record
• not evaluated in context of knowledge of
  medication or other treatment
• the significance of the observations might not be
  clear
• research staff not be in a position to interpret
  the implications.
• information but not interpretation, counseling or
  support.
• For these reasons, UK Biobank will in general
  not provide health information to participants
• UK Biobank Ethics and Governance Framework,
  Version 1.0, 2003

40
Danger of providing information

• Researchers should exercise caution in the
  communication and interpretation of their results
  due to the complexity of genetic information and
  its personal, familial, and social impact.
• RMGA (2003) art. 6

41
(f) Return of results to biological relatives -
International

• immediate and clear benefit to individuals
• avert or minimize significant harm to the
  relevant individuals
• WHO (2003) s.4.3.
• VS
• Investigators should not disclose results of
  diagnostic genetic tests to relatives of subjects
  without the subjects consent
• CIOMS (2002) commentary on guideline 18.

42
Return of results to biological relatives -
National

• Conditions for disclosure to biological
  relatives Canada
• non-disclosure could lead to serious and
  foreseeable harm
• The risk of harm can be avoided through
  prevention or can be controlled through
  scientifically proven treatment
• RMGA (2000) III.3
• United States
• The finding are scientifically valid and
  confirmed
• The findings have significant implications for
  the subjects health concerns, and
• A course of action to ameliorate or treat these
  concerns is readily available
• NBAC (1999) rec. 14

43
Return of results to biological relatives -
National

• Conditions for disclosure to biological
  relatives, continued
• France
• Medical practitioner has an obligation to inform
  the patient of a) the importance to disclose
  relevant information to family members if a cure
  or preventive treatment exists, b) that it is the
  patients responsibility to inform his/her
  relatives Article L1131-1 last paragraph (new)
• Projet de Loi relatif à la bioéthique (adopté en
  deuxième lecture par lAssemblée Nationale),
  n215, session ordinaire de 2002-2003, 10
  décembre 2003

44
Conclusion

• More explicit balancing of rights and of
  advantages and disadvantages taking place both at
  the international and the national level
• Distinction more clearly drawn between refusal of
  access to third parties such as insurers or
  employers (to come) and the legitimate needs (in
  prescribed circumstances) for communication to
  biological relatives
• Still significant variation in approaches taken,
  both at international and at national levels

45
A.II Informed Consent The Process

• Points of view of participants/families/
• ethics committees

46
Ethics as appearing in publications about
geneticsWork of Soumia Essaket, Health Ethics
Diploma, Toulouse, 2004

• Aim Are ethical issues and their management
  mentioned in publications about human genetics
  research in relation with the legal framework?
• Methods a corpus of 168 articles on human
  genetics in populations (with French
  participation) analysed for mention or not of
• Informed consent
• Ethics committee approval
• Acknowledgements and thanks for participants help
• In 2 periods (73 articles, 1987 91 before
  practical implementation of the French law on
  protection of persons in biomedical research and
  95 articles published in year 2000 after

47
Overview on reporting elements of management
related to ethical issues in publications
(Essaket, 2004, unpublished)
48
(No Transcript)
49
Informed consent as seen by research participants
(based on Ducournau, accepted in New Genetics
and Society, 2004)

• Aim a typology of attitudes towards informed
  consent
• Method a qualitative analysis based on 50
  interviews of participants in a research
  case/control study in genetic epidemiology of
  cardiovascular diseases involving a biobank
• Results
• a gradient of various attitudes from support and
  trust to negative perception and distrust
• Influence of previous experiences of relations
  with the medical world

50
Critical appreciation of consent by participants
are distributed at the margins of a continuum of
logic of action
Non-criticising comments. Procedure as "a ritual
of trust" "Hybrid" attitude made of (1)
attention paid to the individual conditions of
participation and (2)collaboration in favour of a
cause.
Criticisms Procedure is felt as in contradiction
with the recognition of the generous
participation act Gift attitude towards medical
progress, collectivity.
Criticisms. Procedure felt as an obstacle to the
construction of trust Strategic conduct,
coupled with a mistrust toward medical profession
or medical institutions
Adapted from Ducournau, 2004
51
Conclusion on informed consent

• It is indispensible
• Who or what does it protect?
• It has to be as prospective as possible in
  terms of long term research giving options is a
  good option!
• It is an evolving process
• It is not a magical tool
• Its limits must be recognised
• Its main feature is that it plays its role when
  it is an instrument of dialogue

52
B.I Use(s) of Biobank Materials

• Typology of biobanks

53
General Context

• Biobanks have existed for long but their use (in
  genetic studies) evolves and increases
• Several levels of considerations in biobanking
• technical issues (70s)
• ethics and legal issues (80s)
• economical and strategic issues (90s)
• institutional and political issues (2000...)
• Lots of work available on ethics, principles,
  recommendations
• Less data on practices, actual situations in
  Europe

54
Persons, Samples and Data

• Biological samples (different kinds)
• Information attached to the sample a priori
  (personal, medical)
• Information attached to the sample a posteriori
  (Ex resulting from a lab test)
• Information non attached to the individual
  samples (Frequencies of markers in a population)
• 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

55
Actors and their context
Commercial Interests
Ethical principles Legal regulation
Scientist(s)
Donors
Medical Applications
Information Cooperation Integrity
56
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
57
Different practical situations 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!

58
The variety of biobanks in Europe Some
information from an EU funded project
Eurogenbank

• The aims were
• 1) to acquire information on the organisational
  and economical aspects, in a variety of biobanks
• 2) to make a typology of the different situations
  actually encountered in several European
  countries
• 3) to investigate the way ethical implications
  were dealt with in various contexts.

Consortium of 15 teams in 9 countries BIOTECH EU
Contract  N BIO4-CT98-0570 Hirtzlin et al. Eur
J Hum Genet, 2003, 11475-488
59
Sampling of structures involved in human genetic
biobanking performed for EUROGENBANK in 6 EU
countries

• Data obtained through
• a general overview in 9 EU countries
• an empirical survey in 6 EU countries
• (UK, France, Germany, Netherlands, Portugal,
  Spain)
• Total 147 structures with human biobanking
  activity explored by questionnaire and interviews

Public or private non for profit Private for
profit
60
Questionnaire structure and items

• 60 questions in 10 sections 200 variables
• Information on institution
• Description of collections
• Mode of acquisition
• Work done on samples and its cost
• Characteristics of storage
• Ownership, exchanges and distribution
• Dissemination of information
• Computerisation and data management
• Difficulties encountered
• Present and future organisation

61
Some features

• Key role of public structures of research or/and
  healthcare
• Biobanking activity is increasing in all the
  countries
• The size of collections is variable, with often
  lot of small collections and few very large ones
• Specific budget is rarely allocated to biobanking
  activity in non dedicated structures
• Very diverse level of precision in consent forms
  (1990)
• A European legal and ethical harmonisation could
  facilitate the growing international
  collaborations in biobanking but questions
  remains about its feasibility.

62
Typology issued from the survey Six main types
of human biobanks

• Relevant criteria
• Public Private status of institution
• Size of collection
• Age of collection and date of start
• Purposes
• Level of openess
• Specific budget identified
• Costs and tariffs

63
Current situation

• Biobanking is an ancient but lively, growing and
  strategic activity in Europe
• Its rather loose organisation, when at small
  scale, is not adapted to forthcoming large scale
  projects
• Professional biobankers are appearing need
  education
• Budget identification and sustainability are
  important and goes parallel with less flexibility
• Challenge to face in building up standards
• to work out an optimal organisation in respect of
  ethical principles,
• to allow the continuation and use of the large
  variety of biobanks that have proven to be very
  useful for many years.

64
Specific points related to genetics in population
using collections of samples and data

• Access to healthy population, not always in
  relation with medical purposes or in a medical
  research context do not harm is not enough
• Search for large sample size at population level
• Heterogeneity of consent/assent Individual
  informed, enlarged consent, opt out, group
  consent
• Work that will be done over years on the same
  samples not always known precisely at the time of
  sampling
• Work at international level, with various
  regulatory texts in the various countries
  Different cultural contexts, values and views
• Kind of results to be returned (general,
  individual, how)
• Sample and data banks ownership
• Transfer of samples and data between research
  groups (level of protection, control on use?)
• Interest of industrial groups in collected
  population samples and benefit sharing

65
A Problem population genetics done in Europe

• Indian ethical bodies and research council are
  complaining that genetic research has
  been conducted in Europe on Indian - possibly
  illiterate tribal- population, possibly without
  asking for proper informed consent and also with
  no benefit for Indian researchers or Indian
  population (benefit sharing)
• EU funds used as well as NIH. This is the first
  case in which the EU is blamed. More cases are
  known until now of US origin.
• Criticisms are
• No Indian institution or scientists are
  mentioned  
• No mention is made of the necessary research
  clearances.

66
A controversial case not unique?

• The Genetic Heritage of the Earliest Settlers
  Persists Both in Indian Tribal and Caste
  Populations T. Kivisild et al.
• Institutions of authors in Estonia, UK, Germany,
  Russia, Kuweit, Stanford
• Am. J. Hum. Genet. 72313332, 2003
• After informed consent was obtained, 180 blood
  samples were collected from healthy and
  maternally unrelated volunteers belonging to
  Chenchu and Koya tribes from Andhra Pradesh,.. 

67
B.I Use(s) of Biobank Materials

• Confidentiality/ Access/ Secondary Uses

68
Different practical situations 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
• Adults or minors or other situations
• healthy or disease affected

69
Use(s) of Biobank Materials

• (a) Confidentiality
• advantages of anonymity
• disadvantages of anonymity
• recommendations
• (b) Access
• (c) Secondary Uses
• waiver of consent
• blanket consent
• Conclusion

70
(a) Confidentiality Level of identifiability of
data

• Advantages of anonymity
• Secures absolute confidentiality
• Eliminates harms associated with secondary uses
  of information

71
Confidentiality Level of identifiability of data

• Disadvantages of anonymity
• Sample cannot be linked to the subjects medical
  record, greatly reducing its value over time
• If research uncovers information from which the
  subject would benefit, it will not be possible to
  convey it to the subject or his/her physician
• If the subject withdraws from the study, it is
  not possible to destroy the sample

72
Confidentiality

• Use the most secure level of identifiability of
  data which allows the research to take place.
• UNESCO (2003) art. 14(e)
• WMA (2002) art. 24
• CE (2002) art. 9
• AMA (2002) art. 4
• RMGA (2003) rec. 4

73
Confidentiality

• Using either the identified information model
  or the permanent anonymization model for
  controlling the flow of information to the
  researcher is problematic and would require
  special justification. The choice between
  double-coding and single coding is perhaps
  somewhat less clear-cut.
• Consortium on Pharmacogenetics (2002) Research, F.

74
(b) Access

• Generally no disclosure to third parties without
  subjects consent
• UNESCO (2003) art. 14(b)
• Barriers to access by third parties (insurers,
  employers, educational institutions) can be
  achieved in two ways
• Directly proscribed (e.g. WHO (2003) s.6.1)
• Indirectly limiting purpose (CE (1997) art. 12)

75
(c) Secondary uses Waiverof consent

• WHO (2003) rec. 10
• Allows for the use of left-over samples when
  anonymized and provided no future identification
  is possible of the samples source
• HUGO, CIOMS, UNESCO
• Allow for the use of stored samples and data in
  coded form provided certain conditions are met
• Continued

76
Secondary uses Waiverof consent

• Conditions
• HUGO (1998) For samples leftover from routine
  medical care
• General notification of such a policy
• Patient has not objected
• CIOMS (2002)
• Minimal risk
• Secondary use expected to yield significant
  benefits
• Secondary use could not realistically or
  reasonably take place were consent requirements
  to be imposed
• UNESCO (2003)
• Consent cannot be obtained
• In accordance with national law
• Proper ethical oversight

77
Secondary uses Blanket consent

• Participants should be informed of the
  possibility of future uses of data, beyond the
  limits of the present consent, and should be
  provided with an opportunity to withhold consent
  to such uses
• WHO (2003) rec. 6(8).
• Informed consent may include blanket consent
• HUGO (2002) rec. 4(a).
• A reasonable policy is to secure a degree of
  flexibility by allowing the subject to consent to
  a range of related studies over time
• Consortium on Pharmacogenetics (2002) Research, B.

78
Conclusion

• Trends
• (1) allowing for the possibility of deviating
  from the traditional principle of explicit
  re-consent for future use of samples collected
  for a specific research purpose as long as the
  privacy/confidentiality of the research sample is
  ensured
• automatic anonymization of samples as the
  expedient solution to the ethical and legal
  quandaries is being re-examined and coding is
  emerging as the preferred option in many
  situations
• Continued

79
Conclusion

• (3) wholesale prohibition of general/blanket
  consent to future unspecified uses of both
  research samples and left-over samples from
  medical care without a specific consent is
  increasingly nuanced and growing recognition of
  the ethical validity of broad or general consent
  to genetic research or banking especially for
  longitudinal studies.

80
B.II Future of Biobanks

• International Directions

81
Future of Biobanks International Directions

• Introduction
• (a) Benefit-Sharing
• (b) Databases
• (c) International Collaboration
• (d) International Harmonization

82
Universal Declaration on the Human Genome and
Human Rights, UNESCO, 1997.

• Genome common heritage of humanity
• Respect individuals uniqueness and diversity
• Non-commodification of the human genome
• Benefit-sharing
• Freedom of research
• Solidarity
• International co-operation

83
(a) Benefit-sharing

• All humanity share in, and have access to, the
  benefits of genetic research.
• Benefits not be limited to those individuals who
  participated in such research.
• Prior discussion with groups or communities on
  the issue of benefit-sharing
• Even in the absence of profits, immediate health
  benefits as determined by community needs could
  be provided.
• At a minimum, all research participants should
  receive information about general research
  outcomes.
• Profit-making entities dedicate a percentage of
  their annual net profit to healthcare
  infrastructure and/or to humanitarian efforts
• HUGO Ethics Committee, Statement on
  Benefit-Sharing, 2000.

84
Benefit-sharing

• In all circumstances, the provision of
  research materials, including DNA samples, should
  be on the undertaking that some kind of benefit
  will ultimately be returned, either to the
  individual from who sic the materials were
  taken, or to the general class of person to which
  that individual belongs.
• Genetic Databases Assessing the benefits and the
  impact on human patient rights, WHO, 2003, rec.
  19.

85
Benefit-sharing

• benefits resulting from the use of human
  genetic data should be shared with society as a
  whole and the international community.
• International Declaration on Human Genetic Data,
  UNESCO, 2003, art. 19(a).

86
(b) Human genomic databases

• Human genomic databases are global public goods.
• Statement on Human Genetic Databases, HUGO Ethics
  Committee, December 2002, rec. 1.

87
(c) 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.

88
International collaboration

• foster international medical and scientific
  cooperation and ensure fair access
• foster the international dissemination of
  scientific knowledge and scientific and cultural
  cooperation
• establish cooperative relationships
• International Declaration on Human Genetic Data,
  UNESCO, 2003, art. 18.
• See also European Commission, The 25
  Recommendations on the ethical, legal and social
  implications of genetic testing, 2004, rec. 21.

89
International collaboration

• Recommendation That
• The European Commission promotes opportunities
  for dialogue between stakeholders to support
  exchange of experience throughout Europe on
  issues of sample and data use for research, at
  the individual, family and population level.
• The European Commission funds multidisciplinary
  research into the ethical, legal and social
  issues related to informed consent procedures for
  human genetic research and other relevant areas
  essential for any evolving research in genetics.
• The 25 recommendations on the ethical, legal and
  social implications of genetic testing, European
  Commission, 2003, rec. 23.

90
(d) 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)

91
Internationalharmonization

• This report endorses the universalisability
  of human rights, and it is considered that its
  recommendations equally enjoy this quality.
• whether funding comes from a public, private or
  voluntary source, all research should be subject
  to the same ethical scrutiny.
• Genetic Databases Assessing the benefits and the
  impact on human patient rights, WHO, 2003 ss.
  2.3, 7.2.

92
International harmonization

• The challenge to international research ethics
  is to apply universal ethical principles to
  biomedical research in a multicultural world with
  a multiplicity of health-care systems and
  considerable variation in standards of health
  care.
• International Ethical Guidelines for Biomedical
  Research involving Human Subjects, CIOMS, 2002,
  Introduction.

93
International harmonization

• P3G Objectives
• Connect the leading public population genomics
  projects
• Provide necessary coordination, harmonization and
  standardization so the combined results be used
  for the advancement of science around the world
• Develop common understanding of the socio-ethical
  and legal issues
• Foster a deeper understanding of the relative
  contribution of genetic and non-genetic
  determinants to health and disease
• Transfer this knowledge to the international
  community so as to optimize benefits for public
  health
• http//www.p3gconsortium.org/

94
B.II Future of Biobanks

• Modelling and Current Directions

95
Policy statements of E S H G Public
Professional Policy Committee (PPPC)

• ESHG. Data storage and DNA banking for biomedical
  research informed consent, confidentiality,
  quality issues, ownership, return of benefits. A
  professional perspective.
• Background document and recommendations of the
  Eur Soc Hum Genet. 2001
• http//www.eshg.org/PPPC.htm
• Eur J Hum Genet, 2003, 11, 906-908

Eurogapp EU project (Co-ordinator S Aymé)
96
OECD task force

• OECD. Biological Resource Centres Underpinning
  the Future of Life. Sciences and Biotechnology
• OECD Code 932001041E1. 2001.
• http//oecdpublications.gfi-nb.com/cgi-bin/OECDB
  ookShop.storefront/EN/product/932001041E1
• A working group is preparing rules that have the
  ambition to become international standards (all
  domains specific by domain)

97
Definition OECD 1999 Tokyo workshop on BRC, 1999
Biological Ressources Centres

•  Biological Ressources Centres are an essential
  part of the infrastructure underpinning
  biotechnology. They consist of service providers
  and repositories of the living cells, genomes of
  organisms, and information related to heredity
  and the functions of biological systems. BRC
  contains collections of culturable
  organisms (e.g. micro-organisms, plant, animal
  and human cells), replicable parts of these (e.g.
  genomes, plasmids, viruses, cDNAs), viable but
  not yet culturable organisms, cells and tissues,
  as well as databases containing molecular,
  physiological and structural information relevant
  to these collections and related bioinformatics 

98
A specific professional society for
biorepositories

• ISBER International Society for Biological and
  Environmental Repositories http//www.isber.org
• Meeting for first time in Europe this year
  (Perugia, Italy, October 17 20, 2004)

99
National ethics committees, European group of
ethics (EGE), Council of Europe (CDBI), UNESCO
Int Bioethics Committee (IBC)

• Several national ethics committees have or are
  currently preparing an opinion related to
  biobanking (France 2003, N 77,
  http//www.ccne-ethique.fr/english/start.htm
  Germany 2004, http//www.ethikrat.org/stellungnahm
  en/stellungnahmen.html)
• EGE opinion 11 in 1998 on tissue banking
  opinion 19 in 2004 on Cord blood banking
  http//europa.eu.int/comm/european_group_ethics/in
  dex_en.htm
• CDBI of Council of Europe preparing in 2004 an
  additional protocol to the Convention on Human
  rights and biomedicine about Human sample use in
  research http//www.coe.int/T/E/Legal_affairs/Lega
  l_co-operation/Bioethics/
• The IBC (UNESCO) has adopted in Oct 2003, an
  International Declaration on Human Genetic
  Databases (including samples)
• http//portal.unesco.org/shs/en/ev.php_at_URL_ID188
  2URL_DODO_TOPICURL_SECTION201.html

100
Assessing the use of biobanks CAMBON-THOMSEN A,
Nat Genet, 2003, 34, (1) 25 - 26

• BIF Biobank Impact Factor. Why?
• Need of long term recognition
• Need of sharing resources outside specialised
  circles
• Need of connecting the use of biobanks with the
  results and impact of research
• Need to find and justify resources for biobanking
• Presently no quantitative parameter
• How?
• Standardise way of citation of biobanks used, in
  publication
• Tracking by ISI
• Choose parameters very carefully
• Over time BIF would become a more rational
  measure of the impact than  reputation 

101
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 Nature Reviews
Genetics, 2004 (in press)

• 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?

102
Towards Biobank-omics
Donors interest views
Population genetics Genetic epidemiology Genes
involved in diseases process Pharmacogenetics Phar
macogenomics
Organs, cells, DNA
transplant
products
regeneration
DNA-sequences

103
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

104
Actors and their context
Commercial Interests
Ethical principles Legal regulation
Population debate, information bodies
Scientists
Donors
Medical Applications
Information Cooperation Integrity