Biobanking Activity

advertisement
Medicel (AOECS 2011)
PATIENT FIRST – AT THE CENTER
BIOBANKING
Thomas M Attard MD FAAP FACG
Associate Professor of Pediatrics, Physiology
The University of Malta Medical School
Consultant Pediatrician, Gastroenterologist
Mater Dei Hospital, B’Kara, Malta
What is a Biobank?
“A collection of biological material and
the associated data and information
stored in an organised system, for a
population or a large subset of a
population.”
Organisation for Economic Cooperation and Development
(OECD)
Why do we need a Biobank?
• Medicel → consortium of pediatric gastroenterologists from
Mediterranean & Surrounding Countries
• Represented countries face challenges re. unique population,
diversity of cultures and evolving resources
• Way ahead includes studying our unique population
• A biobank through integration of molecular data with the clinical
information represents a single, organized, common resource that
can be utilized to perform multiple hypothesis-driven studies,
interface with industry and monitor the evolution of CD in our
societies
Advantages of a Biobank
• Statistical Power
– Large number of samples collected over years but available instantly
• Cost
– Reduces costs, as once collected the collections remains available for a
number of studies
– Harmonised standard operating procedures and best practice yields a more
efficient and time-saving collection of samples which are quality assured
• Logistics
– greater potential for translational research projects and will facilitate
clinical trials.
– development of centralised IT infrastructure creates access for many more
users -incentive to collaborate.
• Ethics
– Single ethical approval and well controlled ethical processes – lessens the
time in setting up the individual biobank as well as strengthens client trust
Population
• Two large groups of Biobanks
– Whole population
– Subset of population
• Whole population
– Collection of samples from a large number of the general population
– Not disease specific
– Useful for epidemiological studies as well as prospective studies
• Subset of population
– Collections from a subset of the population with specific conditions
– Includes family collections
– Useful to identify the causes (both genetic and environmental) of the
condition
– This is the type that is most of interest to our group
Biological Material
• Any biological material can form part of a biobank
• Most common include:
– Fixed tissue samples
• similar to the pathological biobanks present in most of the World’s
hospitals.
• tissue is usually derived from pathologically altered tissue and is
usually fixed.
• advent of new molecular biology techniques and the ability to isolate
single cells from the fixed tissue, both abnormal and normal DNA as
well as RNA information is available.
• information on the protein structure is severely limited and it is not
possible to obtain living and thus reproducing cells from the fixed
tissues.
– DNA/RNA banks
• genetic material (DNA or RNA), usually isolated from white blood cells,
or from other donor tissue.
• stored either as deep-frozen (DNA or RNA) or as dry samples (DNA)
for a relatively long period of time.
Biological Material (Cont’d)
– Body Fluids
• Storage of body fluids (plasma, serum, cerebrospinal fluid, urine)
usually at very low freezing temperature (< -80oC)
• Useful to identify fluid composition at a point in time
– Cell culture banks
• Consists of donor samples (usually blood cells but could also be
any other living, nucleated cells) are transformed into permanent
cell cultures.
• They are usually stored in very low freezing temperature (usually
under liquid nitrogen) and thus, at least theoretically, constitute an
inexhaustible source of DNA of almost unlimited durability.
• They can also be utilised to study gene function, expression and
cellular functions.
Organisation of Samples and Data
• Samples need to be organised in a way that
they can be easily identified and withdrawn
from bank
• Use of well designed storage area
• Organisation of data
– Standardised design
– Electronic database
– Control on data accesibility
Population
Patient
Personal
TISSUE
DATA
Demographic
Clinical
Biobank
research product
Organization –
Storage
Retrieval
Analysis
Multisite Organized BIOBANK(s)
INFORMATION
Identifier
PRIVATE /
(local) primary
investigator
Demographic
CONSORTIUM
Biologic material -TISSUE
Clinical
PUBLIC
ANALYTICAL INFRASTRUCTURE:
•Advanced methods of tissue analysis
•IT support
•Coordinate research
•Interface with Industry
Storage:
•Local
•National
•Regional
•Central
Consortium
protocol
samples
Investigator
/ institutional
samples
Requirements for a Successful Biobank
Infrastructure - Blood
Storage
Use
Pro
Con
Dry Sample on Filter
paper
Room Temperature
• DNA analysis
• Protein/Amino Acid
• Relatively small storage
space
• Easily obtained
• Can remain viable for
decades
• Sensitive to humidity
especially fungal attack
• Requires adequate drying
at sampling time
• Amount of tissue limited
Whole Blood
-20 oC
• DNA analysis
• Limited use for
protein/amino acid
• Easily obtained
• Can remain viable for
decades
• Relatively large quantity
of DNA
• Relatively large storage
space
• Moderate expense in
adequate sample tubes,
freezers, ancillary equipment
and energy costs
Serum
-80 oC
•
• Easily obtained
• Can remain viable for
decades
• Relatively large quantity
of serum for analysis
• Large storage space
• Large expense in adequate
sample tubes, freezers,
ancillary equipment and
energy costs (especially in
tropical and subtropical areas
- require adequate
environmental cooling)
Protein/Amino Acid
Requirements for a Successful Biobank
Infrastructure - Living Tissues
Stored as:
Use
Liquid Nitrogen Viable cells that
Storage
can be grown.
-196oC
Pro
Con
• Can remain viable
for decades
• Practically
unlimited supply of
tissues
• More difficult to
obtain tissues
• Requires fast
processing
• Large expense in
adequate sample
tubes, liquid nitrogen
or freezers, and
ancillary equipment
Requirements for a Successful
Biobank
• Information Technology
– Adequate database containing the fullest data possible
– Adequate security measures in place to safeguard data
protection
– Easy protocols to share data between researchers
– Adequate measures to identify ownership as well as
recognition
• Laboratory facilities
– Medium level – sample preparation
– High Level – for advanced analysis
European Initiatives
• Various local/national biobanks
• Need to harmonise
• Best setup:
– Actual biobank situated at local level
– Centralised (with mirroring and backing) IT
infrastructure available through a web based
interface
– Regional advanced laboratory facilities
• This was identified by the EU - setup of
BBMRI
BBMRI - Biobanking and Biomolecular
Resources Research Infrastructure
• Funded by EC through ERIC (European Research
Infrastructure Consortium) legal entity.
• 53-member consortium with over 280 associated
organisations (largely biobanks) from over 30
countries - largest research infrastructure project in
Europe.
• will form interface between specimens and data and
top-level biological and medical research.
– achieved through a distributed research infrastructure
with operational units in all participating Member States.
BBMRI Participants
Ethical Considerations
Informed consent of the donor
• a universally acceptable principle.
• implies that the person has the “capacity to give
consent.”
• “capacity to give consent”
– to understand the purposes, nature, significance and
implications of the measure calling for consent,
– believe that information;
– to weigh the pros and cons and
– to exercise the right of self-determination in the light of
the understanding arrived at.
Ethical Considerations - Consent
• Types of Consent:
• ‘Blanket’ consent
• Limited Consent:
– Consent to recruit into biobank
– Consent for particular study
– Consent for future studies
– Consent for particular types of future study egs.
Genetic / lab – diagnostic / academic vs. industry
– Consent to be contacted re. future studies
» Default accept / decline participation?
Ethical Considerations
Data Protection
• Ability to trace back the identity the donor can be an
issue where the samples are not anonymized
• various methods by which the data can be coded:
– Direct identification
– Coded - identifiable data is physically separated from the personal
data but the procurer of the sample has access to the code
– Encrypted - third party persons transform the code into a number of
characters, thus identificable by third party
– Anonymized - connection between the code and the identifiable
data is completely lost
– Anonymous - samples were donated in a completely anonymous
form → no personal identifier data
Ethical Considerations
Secondary Use of Stored Tissues
• ability to use the tissues for a research not anticipated for when the
tissues were originally harvested.
• Ideally all research on archival material should have had prior consent for
that study, in actual fact in most cases not available and not feasible to
obtain .
• As yet no consensual agreement on this ethical issue – range from very
rigid approach - no studies can be undertaken on archival material unless
with prior consent to more flexible approach where the decision based on
–
–
–
–
the traceability or otherwise of the person,
the possible anticipated use as compared to the original use,
the risk implications of the research on the individual and
the type of consent at the time of collection.
• A common thread is that there is a need for an approval from an
independent committee.
Ethical Considerations: Commercialisation of
stored biological tissue and Remuneration
• EU Member States adhere to the principle that
donations of human tissues must be free,
– only compensation to cover travel expenses and
loss of earnings.
• In general information generated from studies on
donated tissues belongs to the researcher or team
that creates it and that the individual who may have
been a subject of the research has no legal
entitlements to that research - but by far this view is
not universal.
Ethical Considerations:Genetic
discrimination and stigmatisation
Genetic discrimination
• Person’s genetic background resulting in unequal treatment
• particularly so when applied to employment and insurance contracts.
• This risk is increased where large volumes of data are assembled, as in
biobanks.
• addressed by adequate legislation as well as ethical guidelines.
Genetic stigmatisation
• Stigmatisation is a problem of perception by others or self – difficult to
legislate on.
• Carrier individuals might be classified - stigmatisation
• impact on the donor’s relatives of any identification of genetic disease.
Donor is protected by proper consent guidelines, relatives and even entire
groups of people, who have no previous knowledge of the genetic disease,
might find themselves the recipient of this information and may not wish
to possess it.
Conclusion
• Biobanks are useful to as a research tool
• Reduce the time and expense of research
• Should be set up in a collaborative way were
infrastructure is shared
• Requires robust legal and ethical regulations
which
• Idea of regional hubs should be encouraged
Acknowledgements:
• Prof. Chris Scerri Univ.
of Malta
• AOECS 2011
Download