the european perspective on ethics in biobanking and genetics
TRANSCRIPT
12-13/09/2002 A. Cambon-Thomsen ESF Workshop Biobanks, Uppsala.
A. Cambon-Thomsenand the EUROGENBANK consortium* co-ordinated by JC Galloux2
1. Inserm U 558, Toulouse, France 2. University Paris 2 and University of Versailles Saint Quentin, France
*Lisboa, P: P Lobato de Faria, Central Lancashire, UK : R Chadwick, ZADI - Bonn, D:F Begemann, CPRO-DLO – Wageningen, NL: B Visser, Siena, I: CM Mazzoni, Nordic Gene Bank – Alnarp, S: E Thörn, BRG - Paris, F: A Sontot and Inra - Grenoble, F: M Trommetter, Lünenburg, D: J Simon, Torino: A Piazza, Helsinki, FI: A Sajantila, INIA – Lisboa / EAN - Oeiras, P: E Bettencourt, Barcelona : J Bertranpetit
BIOTECH EU Contract : N° BIO4-CT98-0570
Contact : [email protected]
An empirical survey on biobanking in human genetics in six EU countries
The European perspective on ethics in biobanking & genetics
12-13/09/2002 A. Cambon-Thomsen ESF Workshop Biobanks, Uppsala.
New results New questions
Acquired results
• Genetic component of a disease elucidated
• Genetic component of common diseases
• Population genetics new tools
• New polymorphisms
• Genetic material and DNA
collections
Problems posed
• Which prediction? Why? How to use it?
• Place of genetics in health programmes?
• Ethical and organisational aspects
• Which markers to choose?
• Ethical aspects and how to
manage them?
12-13/09/2002 A. Cambon-Thomsen ESF Workshop Biobanks, Uppsala.
Basic remarks
• History of genetics• Genetic diversity
– Its study opens on the past and on the future
• Characteristics of (human) genome– Common human patrimonium (cf UNESCO
declaration)– Unique characteristics of the individual
• Component of the human body which can be considered at the same time as the most private and the most shared one
12-13/09/2002 A. Cambon-Thomsen ESF Workshop Biobanks, Uppsala.
Genetic material and genetic information
• 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
12-13/09/2002 A. Cambon-Thomsen ESF Workshop Biobanks, Uppsala.
Context of the survey
• Biobanks have existed for long but their use in genetic studies evolves and increases
• Several levels of considerations in biobanking : – technical issues– ethics and legal issues– economical and strategic issues– institutional and political issues
• Lots of work available on ethics, principles, recommendations
• Less data on practices, actual situations in Europe: A European EU funded project with an empirical survey : EUROGENBANK 1999 - 200;1Co-ordinator : JC Galloux
12-13/09/2002 A. Cambon-Thomsen ESF Workshop Biobanks, Uppsala.
General Ethical principles
• Respect of human dignity, beneficence, non-maleficence, justice: – Autonomy– Privacy– Physical and individual integrity – Human body inalienable and unavailable – Equality– Freedom
12-13/09/2002 A. Cambon-Thomsen ESF Workshop Biobanks, Uppsala.
Translation of ethical basic principles into actions
• Ethical principles for protection of individuals participating to research and collections : – Informed consent (not that simple!)
– Non commercial use of human body elements…….
– Confidentiality and protection of private life
– Limitation of genetic testing to medical use or research with ethical committee agreement
• Some countries have specific bioethics laws
12-13/09/2002 A. Cambon-Thomsen ESF Workshop Biobanks, Uppsala.
International texts and guidelines
Nuremberg Code (1947). Helsinki declaration (1964, 2000). Directives from WHO. (Manille, 1981). Recommendations HUGO (1996, 1998, 2000). Convention of Council of Europe ( Oviedo, 1997). UNESCO declaration (december 1997). Recommendations ESHG (2001). Current US texts (BAC) in USA ….
12-13/09/2002 A. Cambon-Thomsen ESF Workshop Biobanks, Uppsala.
Useful references of web sites
• Council of Europe : – www.coe.fr/cm/ta/rec/1990/90/3.html– www.coe.fr/fr/txtjur/164fr.htm
• Other international texts or access to texts: – ASHG : www.faseb.org/genetics/ashg/policy/pol-25.htm– UNESCO : www.unesco.org/ibc/fr/genome/projet/index.html– WHO 1998 : www.who.int/ncd/hgn/hgnethic.htm– HUGO : www.gene.ucl.ac.uk/hugo/conduct.htm
“ “ “ “ /sampling.html– HGDP : ww.stanford.edu/group/morrinst/hgdp/protocol/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 at : www.rmga.qc.ca
12-13/09/2002 A. Cambon-Thomsen ESF Workshop Biobanks, Uppsala.
Specific points related to genetics in population (1)
Access to healthy population, not always in relation with medical purposes or in a medical research context
Search for large sample size at population level Individual informed consent versus group consent Work at international level, with various regulatory
texts in the various countries Different cultural contexts Kind of results to be returned
12-13/09/2002 A. Cambon-Thomsen ESF Workshop Biobanks, Uppsala.
Specific points related to genetics in population (2)
Sample and data banks Exchanges between research groups of samples
and data Interest of industrial groups in collected population
samples Work done over years on the same samples not
always known precisely at the time of sampling.
12-13/09/2002 A. Cambon-Thomsen ESF Workshop Biobanks, Uppsala.
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…)
• Progressive non planned collection• Planned organized collection +/- open
12-13/09/2002 A. Cambon-Thomsen ESF Workshop Biobanks, Uppsala.
Different practical situations (1)Source of samples /data
• Use of existing samples /data : – obtained in situations of health care
– obtained in situations of “donation” (blood, sperm…)
– obtained in the context of a research project
• Constitution of a new collection of samples and data
12-13/09/2002 A. Cambon-Thomsen ESF Workshop Biobanks, Uppsala.
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– major or minor or
other situations– healthy or disease
affected
12-13/09/2002 A. Cambon-Thomsen ESF Workshop Biobanks, Uppsala.
Criteria of informed consent content(French Huriet-Sérusclat Law, 20/12/1988). (Other laws or proposals)
• Written information given• Aim of the research• Methodology• Duration of research• Risks• Constraints• Ethical committee• Right to participate or not• Right to resign at any time
• Prior consent(88,94)
• Protection of privacy (78, 94)
• Duration of conservation
• Return of results• Exchanges, access• Extension or future
research• Commercial issues• Benefit sharing
policy
12-13/09/2002 A. Cambon-Thomsen ESF Workshop Biobanks, Uppsala.
General difficulties
• Consent for genetic studies has specific features which should be taken into account at an international level (guidelines, model consent at : www.rmga.qc.ca)
• There is no international consensus about how to manage and organise collections of human material for genetic studies (it starts : reports and recommendations at : www.eshg.org)
12-13/09/2002 A. Cambon-Thomsen ESF Workshop Biobanks, Uppsala.
Aims of the survey
• The aims of the European Research Project EUROGENBANK for its human biobanking empirical part 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.
12-13/09/2002 A. Cambon-Thomsen ESF Workshop Biobanks, Uppsala.
Methodology (1)
• The steps were :
1) to make a general overview in each of the countries involved
• on scientific, organisational and economical issues
• on existing ethical and legal regulatory texts
2) to investigate through an empirical survey a number of banks meeting certain criteria
• through questionnaires
• through interviews
3) to make a comparison allowing a typology integrating various aspects
12-13/09/2002 A. Cambon-Thomsen ESF Workshop Biobanks, Uppsala.
Methodology (2)
• Use general overviews to establish criteria for choosing targets for empirical survey
• Design of questionnaire and interview structure• Data capture and definition of variables• Statistical analysis and analysis of contents• Report by country • Comparison : common trends, specific features• Typology• Recommendations
12-13/09/2002 A. Cambon-Thomsen ESF Workshop Biobanks, Uppsala.
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
12-13/09/2002 A. Cambon-Thomsen ESF Workshop Biobanks, Uppsala.
Questionnaire structure and items
• 60 questions in 10 sections 200 variables– Information on institution
– Description of collections
– Mode of acquisition of collections
– Work done on samples and its cost
– Characteristics of storage
– Exchanges and distribution
– Dissemination of information
– Computerisation and data management
– Difficulties encountered
– Present and future organisation
12-13/09/2002 A. Cambon-Thomsen ESF Workshop Biobanks, Uppsala.
Status France Germany Netherlands Portugal Spain United Kingdom
Laboratories withinhospitals or healthinstitutes (public or
private non-for profit)
52.1% 80 % yes 9% 76.1% 58%
Research anduniversity laboratories
10.5 % 20 % yes 82 % 16.7% 17 %
Firms (biotech orpharmaceutical
companies)
13.4 % 0% 0% 0% 0% 0%
Centres for studiesand conservation of
eggs and sperm
7.5% 0% 0% 0% 0% 0%
Blood banks 3% 0% 0% 0% 0% 8%
Patient association 4.5% 0% 0% 0% 0% 0%
Forensic institutions 4.5 % 0% 0% 9% 7.2% 17%
Others 4.5 % 0% 0% 0% 0% 0%
Total Number 67 10 5 11 42 12
Genetic material banking is an activity concerning all kinds of research or health care organisations
12-13/09/2002 A. Cambon-Thomsen ESF Workshop Biobanks, Uppsala.
Purpose France Germany Netherlands Portugal Spain UnitedKingdom
Total
Diagnosis 46 yes yes 7 32 5 >90Familial studies 32 yes yes 9 3 6 >50Polymorphism
characterisation29 yes yes 4 8 5 >46
Epidemiologicalstudies
25 yes yes 6 4 4 >39
Functional studies 29 yes yes 3 0 3 >35Clinical follow-up 26 yes yes 4 0 3 >33Genetic mapping 17 yes yes 3 2 5 >27
Elaboration ofsubstances of
industrial interest
9 ND ND 1 0 1 11
Drug development 8 ND ND 1 0 1 10Pharmacogenomics 8 ND ND 0 0 2 10
Gene therapy 8 ND ND 0 1 0 9Other 0 ND ND 0 0 1 1
How to read? 46 for France means that among the returned questionnaires the use of collections for diagnosis has been evoked 46 times
Uses of collections by country and order of importance
12-13/09/2002 A. Cambon-Thomsen ESF Workshop Biobanks, Uppsala.
Fundingsources(number of banks percountry)
France Germany Netherlands Portugal Spain United Kingdom Total
Global budget ofthe organisation
56 9 5 9 38 5 122
Funding byco-operativeagreement
10 9 0 1 5 1 26
Grants 27 9 0 0 1 3 40Sales 6 0 0 0 0 0 6Unanswered 0 0 0 0 0 4 4Total (doubleentries allowed)
99 27 5 10 44 13 198
Ways of funding Biobanking
12-13/09/2002 A. Cambon-Thomsen ESF Workshop Biobanks, Uppsala.
Ethical issues and points of tension underlined
• rights of persons (autonomy, confidentiality, protection of private life)
• correct information prior consent and old banks
• non commercial use of human body parts
• maximum quality of sample conservation & management
• optimal and transparent use of samples / data for quick progress of knowledge
rights of researchers
developments over the years unclear
development of commercial products samples
easy access to them without complications
rights of priority of primary researchers and companies interests
12-13/09/2002 A. Cambon-Thomsen ESF Workshop Biobanks, Uppsala.
Major trends and common features
• Almost all interviewed structures belong to the public sector or private for non-profit sector
• Public structures of research or/and healthcare have a key role for banking activity
• Banking activity is increasing in all the countries because few samples are discarded and genetic activity is growing
• The size of collections is variable, with often lot of small collections and few very large ones
• Purposes of collections are often research or research and healthcare ; mostly diseases motivate the constitution of collections
• Samples are usually provided free of charges as gift or exchanges
• Very diverse level of precision in consent forms (+++1990)
12-13/09/2002 A. Cambon-Thomsen ESF Workshop Biobanks, Uppsala.
Major trends and common features
• Specific budget is rarely allocated to biobanking activity
• Costs of storage are not often evaluated ; they are small compared to sample manipulation
• Good practice guidelines are generally followed and quality controls performed but quality procedures are not always clearly explained
• Associated data are often computerised ; mostly identity information is linked and samples are identified or traceable
• Biobankers are generally against centralisation of samples but favourable to a centralisation of biobank data
• A European legal and ethical harmonisation could facilitate the growing international collaborations in genetic banking ; but questions remains about its feasibility.
12-13/09/2002 A. Cambon-Thomsen ESF Workshop Biobanks, Uppsala.
Type 1:Smallpubliccollections
Type 2:Largepubliccollections
Type 3:Databases
Type 4:Privatecollections
Type 5:Privatenon forprofit
Type 6:Established bystatus1
Status ofinstitute
Public
Private fornon-profitPrivate forprofit
Size ofcollections
Small
MediumLarge
Age ofcollections
< 5 years
Between 5and 10 years> 10 years
Purposes ofcollections
Health
ResearchHealth andresearchForensicOthers
Openness YesNo
Specificbudget
Yes
NoCost Bad known
Well knownPricing Fee for
serviceGift andexchangeNoexchange
Legend Mostfrequent
Lessfrequent
1 For instance : forensic institute, blood transfusion centre, centre of studies and conservation of sperm…
Typology issued from the survey:
Six main types of human biobanks
12-13/09/2002 A. Cambon-Thomsen ESF Workshop Biobanks, Uppsala.
Proposals drawn from results of Eurogenbank project (1)
• Official recognition and identification of biobanking activity
• Financial sustainability
• Guidelines for quality of collections
• Need of education to biobanking
• Simplification and harmonisation of administrative procedures
• Harmonisation of import/export rules within EU
• Harmonisation of framework for consent forms, further use, gene ownership
• Develop a European view on benefit sharing (HUGO’s considerations)
12-13/09/2002 A. Cambon-Thomsen ESF Workshop Biobanks, Uppsala.
Proposals drawn from results of Eurogenbank project (2)
• Clarify who (or which body) is the interlocutor for biobanking at the EU commission level
• Support to organisation of aspects of biobanking by actors at national or European level
• Only back up at “central” level (duplication)• Organisation of platforms of exchanges• Start projects about the organisation of a
centralisation of data about samples not of samples themselves (databases interconnected)
12-13/09/2002 A. Cambon-Thomsen ESF Workshop Biobanks, Uppsala.
Discussion
• Biobanking is a lively, growing and strategic activity in Europe, practised in numerous sites for a long time
• Its rather loose organisation, when at small scale, is not adapted to forthcoming large scale projects
• Professional biobankers are appearing• Budget identification and sustainability 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.
12-13/09/2002 A. Cambon-Thomsen ESF Workshop Biobanks, Uppsala.
ConclusionsConclusions
• Genetic material collections and population studies are one of the aspects of human genetics generating issues of general relevance in human genetics
• Relations between different aspects of human genetics• Symbolic dimension of human genetics in society• Increased accuracy of issues and difficulties at the
international scale• Importance of communication and debate• Question of education of « the public » to genetics but also
of education of future geneticists to ethical issues management