Contents
Page
Introduction
2
Principles
2 – 20
- Informed Consent & Competent Adults & Minors
4–5
- Informed Consent & Mentally Incompetent
5–6
- Information Requirements
7–8
- Consent for Surplus Material
8–9
- Researchers & Medical Information
10 – 13
- Research Participants & Research Results
13 – 15
- Genetic Research – Specific Issues
16 – 18
- Multiple Genetic Testing
18
- “At Risk” Individuals
18
- Pharmaceutical Companies
18 – 19
- Outside EU
19 – 20
Appendix 1: Commentary on Principle No 6
21 – 23
Appendix 2: Terms
24 – 26
Appendix 3: Checklist - Samples of Human Material
27 – 29
Appendix 4: Guide for production of Patient Information Leaflet
30
1
Introduction
This document is intended to be a guide to Research Ethics Committees considering clinical
trials, which involve DNA testing, or genetic sampling. It is the culmination of a conference
held on the 27th February 2002 sponsored by the Irish College of General Practitioners, The
Health Research Board and Irish Medicines Board.
Principles
1.
An appropriately constituted Research Ethics Committee must approve all
research using samples of human biological material.
2.
Research should only go ahead if the potential benefits outweigh any potential
risks to the donors of the samples.1
The risk that information from laboratory tests on a sample might harm the donor or
their interests must be kept in mind.
3.
The human body and its parts should be treated with respect.2
4.
Samples of human biological material obtained for research should be treated
as gifts.3
1
Medical Research Council, Human and biological samples for use in research: Operational and
Ethical Guidelines (London: 2000), p. 3.
2 Medical Research Council, Human and biological samples for use in research: Operational and
Ethical Guidelines (London: 2000), p. 3.
3 Medical Research Council, Human and biological samples for use in research: Operational and
Ethical Guidelines (London: 2000), p. 3.
Researchers have a duty to ensure the donors’ wishes are respected when using the material.
In the UK and probably in Ireland it is not legally possible to own a human body. The law is unclear as
to whether or under what circumstances anyone can legally “own” samples of human biological
material or whether donors of biological material have any property rights over “their” samples. For
human material used in research, the important consideration is not legal ownership, per se, but who
has the right to control the use made of samples or their transfer to a third party. Therefore the term
“custodianship” rather than ownership, to imply responsibility for safe storage of samples, for
safeguarding the donors’ interests, and for the control of use or disposal of the material is used. It is
recommended that tissue samples donated for research be treated as gifts or donations, although gifts
with conditions attached. This is preferable from a moral and ethical point of view, as it promotes the
“gift relationship” between research participants and scientists, and underlines the altruistic motivation
for participation in research. It also provides a practical way of dealing with the legal uncertainty over
ownership, in that any property rights that the donor might have in their donated sample would be
transferred, together with the control of use of the sample, to the recipient of the gift. Gifts may be
conditional (that is, a donor may specify what the recipient can do with a gift), and it is very important
that the donor understands and agrees to the proposed uses of the donated material. The assumption
by the donor is that nothing will be done that would be detrimental to his or her interests, or bring harm
to him or her. If samples taken for research are to be treated as gifts, there must be a recipient, to
whom formal responsibility for custodianship of a donated sample of material is transferred. While the
principal investigator should have day-to-day responsibility for management of a collection of human
material, it is more appropriate for formal responsibility for custodianship of collections of human
material to rest with institutions rather than with individual researchers. This provides greater security
for valuable collections, provides better assurance that donors’ rights will be protected and makes it
easier to deal with changes in individual circumstances of the principal investigator(s). The university,
2
i.
Participants must be told if there may commercial exploitation of any nature of the
samples taken and that they will not be entitled to any profits (unless there is an
agreement to the contrary)
Commentary
 Under ideal circumstances a research steering committee should be established to
act as custodian of genetic research material. The steering group should
include representatives from the research institution involved in the work, the
funding agency, whether pharmaceutical or other, and a named individual
responsible for the conduct of the research i.e. principal investigator. In
situations where it is not feasible to establish a steering committee the research
institution involved in the work should act as custodian of the research
material.
Ideally this committee would need to be active for as long as the material is
stored so the storage period would need to be defined. As storage may be
intended for many years, the formation of a long acting committee might be
problematic.
5.
The human body and its parts shall not, as such, give rise to financial gain.4
6.
Informed consent is required from the donor (or the next of kin, if the donor has
died) whenever a new sample is taken wholly or partly for use in research.
Donors should understand what the sample is to be used for and how the results
of the research might impact on their interests. Consent must also be obtained
for storage and potential future uses of samples.5
hospital or other host institution where the principal investigator is based will usually be the most
appropriate body to have formal responsibility for custodianship of human material donated for
research. When central banking facilities are available, there may be a requirement for the investigator
to split the sample and provide a portion to the bank as a condition of research funding. Valid consent
from the donor will of course be required to share a sample with other researchers in this way.
4 Medical Research Council, Human and biological samples for use in research: Operational and
Ethical Guidelines (London: 2000), p. 3.
Researchers may not sell for profit samples of human biological material that they have collected as
part of their research, and research participants should never be offered any financial inducement to
donate samples. Payment of reasonable expenses or costs is however acceptable. Donors should
be informed if their samples might be used in commercial research. Intellectual property rights (IPR)
arising from research using human samples may be sold or licensed in the same way as other IPR. In
relations to IPRs the EU Directive on the legal Protection of Biotechnological Inventions has now been
brought into force in Ireland by virtue of S.I. No. 247 of 2000. The Directive is further discussed in Sheikh A. A. “‘Owning’ Life: New Frontiers in Patent Law, Genetics and Biotechnology” Medico-Legal
Journal of Ireland 5 (1999) 1: 23.
This point is to be read in conjunction with point 3 above which seems to suggest that provided
patients are informed prior to giving consent that there may be commercialisation of the samples,
there is no specific problem with profits accruing from the research in question. This is important in
terms of ensuring that sponsors who invest heavily in the process of studying genetic material to learn
more about diseases in the hope of identifying new diagnostic techniques and possible treatments
have an expectation of commercial gain if successful. This principle is underpinned by Directive
98/44/EC on the legal protection of biotechnological inventions which permits the patenting of
inventions involving biological material (including genetic material) provided there is an inventive step
involved and the invention is capable of industrial application. Under that Directive, biological material,
even if it previously occurred in nature, or material isolated from the human body or otherwise
produced by a technical process including a sequence or partial sequence of a gene, may constitute a
patentable invention
3
The IMB currently allows the taking of genetic samples, provided separate specific consent is
obtained. Such consent is generally obtained by way of a separate consent form – this permits
the patient to opt out of providing a genetic sample while continuing in the clinical trial if
they so wish.
Informed Consent & Competent adults6
Therapeutic and Non-therapeutic Research
In the case of the competent adult, in cases of both therapeutic and non-therapeutic research,
once there is full disclosure of all facts (in relation to the objectives of the research, the
personnel involved, the procedure involved, existence of alternatives, the side-effects if any
and risks, advantages and disadvantages) to the adult, it will be the adult who will consent by
means of a written informed consent.
Informed Consent & Minors
Therapeutic Research
The consent of an incompetent minor to participate in therapeutic research can be given by a
parent/guardian. The doctor must give full disclosure to the proxy, including the disclosure of
any risks involved. The proxy must also be satisfied that on a reasonable assessment of a
risk-benefit ratio, the treatment is in the best interests of the child.
A minor aged between 16 and 18 years can now consent to surgical, medical or dental
treatment, which includes any procedure undertaken for the purpose of diagnosis, and any
procedure including the administration of an anaesthetic, which is anclillary to any treatment
as it applies to that treatment.
An incompetent minor, for the purposes of ‘surgical, medical or dental treatment’, is one who
is below the age of 16 years. The Act7 may be of relevance to therapeutic research since
diagnosis and treatment may be part of such research. However, due to the fact that such
diagnosis and treatment is still in the form of research, as a matter of good practice and
prudence the consent of a guardian should be required along with consultation and serious
consideration of the views of the minor.
Non-therapeutic Research
The Non-Fatal Offences against the Person Act, 1997, is not relevant for the purposes of nontherapeutic research since such research does not involve diagnosis or treatment but only the
ascertainment of knowledge. Thus, for the purposes of non-therapeutic research, a minor is
5
Medical Research Council, Human and biological samples for use in research: Operational and
Ethical Guidelines (London: 2000), p. 3.
6 A. Sheikh, Genetic Research and Human Biological Samples: The Legal and Ethical
Considerations, (Dublin: Health Research Board, 2002), pp 27-30.
7 Non-Fatal Offences against the Person Act 1997.
4
an individual who is below the age of 18 years. In such cases, again, parental consent or
guardian would be required along with the consultation and consideration of the views of the
minor.
Informed Consent & the mentally incompetent
Therapeutic Research
With regard to therapeutic research consent, the doctor stands as a proxy and is entitled in law
to treat if such treatment is in the patient’s best interest… By this reasoning the doctor may
involve the incompetent adult in therapeutic research if what is to be undertaken is in the
patients’ best interests.8
Non-Therapeutic Research
Non-therapeutic Research on an incompetent adult can be considered, in certain
circumstances, unlawful.9
Such rationale is based on the general reasoning that non-therapeutic research has no ‘benefit’
to a research participant. While this may be accurate in terms of direct benefit in relation to
treatment, to say that non-therapeutic research holds no ‘benefit’ at all to the participant is not
entirely accurate. This is especially so in relation to research into the genetic basis of disease,
since the findings of such research, while not immediately aimed at treatment, therapy or
cure, may give invaluable insights into diseases which my hold indirect benefits to research
participants. The mentally incompetent and minors are primary target groups for such
research since it is those very groups that suffer from certain serious diseases that will be the
target of genetic research. Thus, not allowing non-therapeutic research on those groups may
entirely exclude the hopes of any medical or scientific progress, therapy, treatment or cure at
any future time.
The situation pertaining to donor participation in genetic research (as opposed to treatment)
such as where an individual donates a biological/bodily/DNA sample for the purposes of
research aimed at discovering their genetic basis of disease and where the physician
intervention is minimal, as is any risk, has not been examined by the courts or commented on
by way of legislation. However, in the light of current ethical thinking, it cannot be said
authoritatively or at all that such participation is illegal/unlawful.
Requirements of an Informed Consent10
i.
In the competent adult, consent must be valid, full and written, and signed by an
authorised member of the research team, the participant and preferably by a witness.
ii.
In the case of an incompetent minor participating in non-therapeutic research, a
parent/next-of-kin/proxy can give consent after full disclosure of facts and if the
research carries minimal burden and risk and the process cannot be achieved by other
means.
8
Kennedy & Crubb, Principles of Medical Law, (Oxford: Oxford University Press, 1998), pp 725-726.
Ibid. at 731.
10 A. Sheikh, Genetic Research and Human Biological Samples: The Legal and Ethical
Considerations, (Dublin: Health Research Board, 2002), pp 62-63
9
5
iii.
In the case of an incompetent adult, no other person in law can consent on their behalf,
therefore in non-therapeutic research:
 The opinion of a GP and another appropriate person ought to be sought to ensure
capacity when or if capacity is in doubt families or very close friends may be
consulted.
 The procedure must involve minimal risk, invasion, burden and discomfort.
 The individual must agree to the procedure or it must be made sure that the person
does not object or seem to object.
 The research must be such that it cannot be achieved by any other means.
iv.
Those potential participants where capacity is intermittent should only be approached
during a ‘lucid period’ (when they have capacity). To determine this capacity two
opinions should be sort
v.
Prior to obtaining consent to take a sample:


Individuals must be told of the purpose for which the sample will be used
And researchers must seek permission from the patient if samples are intended to
be used for any other purpose whatsoever at any time (such ‘further use’ is
inadvisable in the incompetent individual participating in non-therapeutic
research).
vi.
Interviews and all explanations especially with a view to or prior to obtaining consent
must be impartial, without force or inducement, and should be conducted in as
sensitive a manner as possible and explained in a language that the potential
participant can understand.
vii.
Any indications that the benefits to the patient are monetary are not acceptable and
should not be mentioned. Expenses for time, expense and inconvenience are of course
acceptable. At all times, the primary benefit is medical.
 At the outset of a research project, a researcher should discuss with the subject the
possibility and/or probability that the genetic material and the information derived
there from may have potential commercial uses. In addition, if the sample is being
handed on to a third party, the subject should give express permission.
viii.
If results are to be fed back to individuals, their consent to a whole range of issues
must be obtained:
 Primary testing
 To any other testing that will be done (having explained what those other
tests may be)
 When researchers are taking samples for genetic studies, the patient needs
to be fully informed on the use to which the sample would be put, whether
any information will come back to the patient on the results of a genetic
test. If results are being issued, then a time scale should be arranged for
delivery of the results to the patient. If samples are being anonymised, the
patient needs to be clearly told of this fact, but yet informed of the general
nature of the testing being carried out.
 Feeding back genetic results to families should only be done after
confirmation by a service diagnostic laboratory. Feeding back research
results alone can be fraught with problems
6
ix.
Participants must be told of privacy protective measures over samples and data:
 Within Ireland and
 Within any other host country; written assurances from the host country must
exist, be shown or available for inspection.11
x.
The participants must have the option of withdrawing at any time
 In addition to the standard withdrawal clause in any information sheet, the
withdrawal clause should include the destruction of the genetic sample, and the
agreement of the researcher to carry out no further tests.
It should be noted that it is not possible to destroy unlinked anonymised samples
as they cannot be traced back to the donor. Furthermore agreement to do no
further testing can only be given for samples that are not anonymised.
7.
Information on Genetic Testing for Participants in Research:
Requirements.12
Information
i.
Is the information, including that on any disorder being tested for - full, accurate
and appropriately presented, in a clear and simple manner that is readily
understandable?
ii.
While some individuals who may be invited to participate in research including
genetic testing will have extensive experience of the condition, personally or in
their family, others will not, or the information may be incomplete. Accurate
information is essential if individuals are to make valid decisions regarding testing.
Written information should be provided in an understandable form, and particular
consideration should be given to providing information to those with hearing or
visual disabilities, the preliterate, or whose first language is not English.
iii.
Where the test is to gain knowledge of the genetic determinants of a known
disorder, the participants will need information on the purposes and implications for
themselves and for their families if there is an intention to feed back results to
participants.
iv.
If there is an intention to feed back research results to participants, clinically
relevant findings should be independently confirmed by a diagnostic genetics
laboratory before such information is given to families, or used clinically.
v.
Information should deal with both the benefits and potential disadvantages to the
individual and/or the potential to increase wider knowledge about genetics.
vi.
While written information is important, complex information should also be
provided face to face by an appropriately trained and experienced person.
11
Future host countries may not always be known at the time the sample is taken. In any case, the
sponsor would be obliged under Directive 95/46/EC on personal data protection to ensure that
information was conveyed to non-EU countries or ‘third countries’ only if such a country also had
satisfactory legislation or practices in place to ensure data protection
12 Advisory Committee on Genetic Testing, Advice to Research Ethics Committees (London: October
1998), p. 9
7
vii.
In genetic testing there are frequently complex and sensitive issues that require
discussion, rather than simply provision of information. While not all such issues
require involvement of specialist genetics services, these have an important role
when they are complex and time-consuming, or when they involve members of the
extended family.
viii.
Where necessary, the Research Ethics Committee may wish to consider whether
appropriate arrangements are in place to ensure that research subjects are suitably
informed. For instance, in specialist genetic practice, genetic counsellors and other
professionals play an important role in pre-test preparation and in post-test home
visiting to ensure that necessary support is explored and that information has been
received and understood.
8.
Patients should always be informed when material left over following diagnosis
or treatment (described as surplus to clinical requirements) might be used for
research. Wherever practicable, and always when the results of the research
could affect the patient’s interests, consent should be obtained to the use of such
surplus material.
i.
When obtaining consent to take a sample of human material for research, it is
important to allow for the fact that it might subsequently be useful for new
experiments that cannot be foreseen. Therefore, unless a sample will be fully used
up for the initial project or cannot be stored, a two-part consent process is
recommended, the donor being first asked to consent to the specific experiment(s)
already planned, and then to give consent for storage and future use for other
research. Unless the sample is to be anonymised and unlinked prior to storage (in
which case this should be explained to donors), it is not acceptable to seek
unconditional blanket consent, for example using terms such as ‘all biological or
medical research’.
If samples may be stored or used in a form that allows them to be linked to
individuals, possible future research should be explained in terms of the types of
studies that may be done, the types of diseases that could be investigated, and the
possible impact of the research on them personally. The benefits of enabling more
efficient use of valuable samples should be explained to donors. For example, a
researcher collecting samples from patients with diabetes might seek consent to store
the samples for future research into the biological basis and treatment of diabetes and
related complications, on the basis that researchers using the sample for secondary
research cannot identify the donor. Researchers undertaking a broader
epidemiological study might seek consent to store samples for future research into
biological or genetic factors affecting the risk of developing a range of common
medical conditions, on the understanding that results of tests done for research
purposes will not have direct clinical implications for the donor. Similarly, donors
must be made aware that other researchers might use their samples, including
scientists working for commercial companies (if appropriate). Participants must be
given the reassurance that all secondary use will require approval by a Research
8
Ethics Committee13, and that no tests of known clinical value for diagnosing or
predicting disease on samples that can be linked to them individually will be done
without their consent. Information for participants should include an explanation of
how any surplus material will be disposed of when it is no longer required in the case
of samples that are not anonymised.
ii.
Where a two-part consent process is used, donors must always be given the option
of specifying that their sample may only be used for the research project already
planned. If consent is obtained to use a newly collected sample for one specific
study only, the only purpose for which it can be re-used is to verify the results of
that study. When no longer required for that purpose it should be destroyed. It is the
responsibility of the custodian to ensure that all uses of a sample are in accordance
with the consent obtained from the donor.
iii.
The special sensitivity of the public with regard to genetics research should always
be taken into account. If there is the possibility that secondary use may include
genetic research, this must be included in the explanation of possible future research
when consent is obtained. There are certain types of genetics research which
currently give rise to particular concern, for instance that relating to personality,
behavioural characteristics, sexual orientation or intelligence. It is particularly the
use of samples in these or other areas of research that are likely to cause special
concern to the donors, even if the samples are to be anonymised and unlinked.
When is it necessary to seek new consent?
iv.
It is of course necessary to seek new consent when collecting new data from
research participants. Consent should also be obtained to access participants’
medical records if this was not done when the sample was originally collected.
Where samples can be anonymised and unlinked before use, no new consent is
required. In some rare circumstances research on linked samples originally taken for
another research purpose may be permissible without consent. An example would
be epidemiological research where the only practicable approach is to use stored
samples and identifiers are needed to link samples and different types of health
records. Before stored samples are used in this way researchers must demonstrate
that contacting donors to seek consent is not possible or not practicable. Old
samples of material surplus to clinical requirements may be used for linked research
without specific consent if there is no possibility that the research could affect the
patients’ interests in any way and if obtaining individual consent is not practicable.
Research Ethics Committee approval is essential for all new research using stored
samples of human material.
13
The Research Ethics Committee needs to consider whether it should be referred back to for this
approval or whether it should recognise approval given by a University, College or hospital based
ethics committee. If the latter is agreed to it will exclude private ethics committees, which some
pharmaceutical companies have funded.
9
9.
There should be a clear separation of the research specimen from service testing
samples.
i.
Good laboratory practice should ensure that whenever practical, a clear distinction
is made between diagnostic testing, i.e. testing a patient to aid in their diagnosis,
treatment and management and genetic testing in the context of medical research.
ii.
If a research subject or their clinician later requests presymptomatic or diagnostic
testing or other genetic services, then it should be normal practice that the request is
considered on its merits and then if accepted a new specimen obtained. This aspect
should be explained to the research subject.
iii.
If the concept of keeping research and `service' specimens entirely separate is not
physically practical then there must be a proper control system in place that ensures
that research samples can be easily identified as such. It will be especially important
to be assured that there is a single high level of quality assurance and test control if
the two aspects are not to be physically separated. 14
iv.
Research Ethics Committees and researchers should be aware that any medical
information to be stored within Ireland is subject to the Data Protection Act 1988,
the Freedom of Information Act 1997, and the EC Directive on the Protection of
Data: 95/46/EC and legislation may have an impact on the use of genetic data.
10.
It should be ascertained whether the pharmaceutical company have plans to
contact patients or retest samples if improved tests for a disorder become
available.
11.
Researchers should treat all personal and medical information relating to
research participants as confidential. This applies as much to the results of
laboratory tests done as part of the research project as to information obtained
directly from donors or from their medical records, People who donate samples
for research must be told what personal or medical information about them will
be used in the research, who it might be shared with, and what safeguards are in
place to protect their confidentiality.15
i.
Personal information provided for health care or medical research is confidential.
Wherever possible people should know how information about them is used.
Researchers should normally have each person’s explicit consent to obtain, store
and use information about them.
Comment:
The term confidentiality is intended to convey that information will not be divulged
to a third party except where this is/may be required by law. In law the exceptions to
confidentiality would be (1) consent expressly given by a competent person, or
14
Advisory Committee on Genetic Testing, Advice to Research Ethics Committees (London: October
1998), p. 5
15 Medical Research Council, Human and biological samples for use in research: Operational and
Ethical Guidelines (London: 2000), p. 4.
10
consent implied from the necessity doctrine in the context of patient care or in cases
of research where the information is anonymised; (2) court order in personal injuries
litigation; (3) where disclosure if in the person’s best interests; (4) where disclosure
is in the public interest (e.g. infectious disease control); (5) where disclosure is
necessary to protect another specific individual – arguably protection of another
affected relative would be covered by this exception, whether or not a cure is
available for the disease. This, of course, raises difficulties with regard to the right
not to know. It may also be argued in this context that the information is not owned
by the person tested but by the family sharing the same gene pool.
ii.
All medical research using identifiable personal information or anonymised data
that is not already in the public domain must be approved by a Research Ethics
Committee.
iii.
All personal information must be coded or anonymised as far as possible and as
early as possible in the data processing.
iv.
Each individual entrusted with patient information is personally responsible for his
or her decisions about disclosing it. Personal information should only be handled
by health professionals or staff with an equivalent duty of confidentiality.
As part of normal monitoring of clinical research, ICH-GCP guidelines require that
personal information may also be disclosed to the trial sponsor (or their agents),
regulatory authorities, trial auditors and Research Ethics Committees. This is
consented to by trial participants.
v.
Principal investigators have personal responsibility to ensure that procedures and
security arrangements are sufficient to prevent breaches of confidentiality.
vi.
At the outset researchers must decide what information about the results should be
available to the people involved, and agree these plans with the Research Ethics
Committee.
vii.
Is it intended that the test results be given to the research subject or added to the
medical record in any circumstances?16
This is a fundamental issue, which may affect a REC's actions on such research
proposals. If the result of a genetic test undertaken as part of a research protocol may
be passed on to the participant or added to the medical record, then that patient must
have been fully informed about the test(s) and prior specific consent sought.
Concern over disclosure is particularly acute where the research involves late onset
disorders, but remains a significant issue in all-genetic testing.
There is clearly a boundary between research and clinical practice which may only
be crossed in the interests of the tested individual, and only with their prior
knowledge and their prior consent (subject to the usual provisions for children etc).
It is important that research protocols address this issue and that Research Ethics
Committee’s are content that the implications of genetic testing for the subject and
their families will be understood by the participants.
16
Advisory Committee on Genetic Testing, Advice to Research Ethics Committees (London: October
1998), p. 6
11
viii.
Where results from research are intended to be, or may be, disclosed does the
information to be provided make clear what use may be made of test results? Where
test results may be disclosed, are the research subjects fully informed of potential
adverse consequences, such as for insurance, employment, and effects on other
family members?17
There is increasing awareness and concern over the possible use of genetic
information by third parties such as the insurance industry. Such issues need
properly to be considered. In addition, genetic testing may also directly or indirectly
have effects on family members who have not themselves been tested or may not
wish to be tested. In some genetic disorders an abnormal result in an individual may
also mean that healthy siblings (or even a healthy parent) may be at risk. Such
implications for other family members must be fully considered in the protocol. It is
necessary to take account of the fact that these individuals may not wish to know
that research involving another member of the family has revealed a genetic result
with an implication for them. This `right not to know' is as important for some as the
`right to know' is for others. The protocol must address these aspects if results are to
be disclosed.
As for insurers, if the volunteer informs the company that genetic tests were done,
then the insurer could have a reasonable case in law to argue for disclosure on
principles of ubberima fide in insurance law. If the volunteer does not inform the
company, then again the insurance contract could later be avoided on the grounds of
misrepresentation/ non-disclosure. With the current moratorium in place by the ABI
until 2003, Irish insurance companies are not seeking this information. Ultimately
the legislature will need to address this issue.
ix.
The strictest safeguards must be instituted to preserve the privacy of genetic
information. Particular cognisance of privacy issues needs to be taken into account
when genetic information is stored in electronic format.
x.
Unless required by law, there should be no compulsion on, or coercion of, the
person, the attending doctors or staff of a genetics laboratory or register to
acknowledge or in any other way to reveal that a genetic test has been undertaken,
or to divulge the results of any test which may have been undertaken.
In law the exceptions to confidentiality would be (1) consent expressly given by a
competent person, or consent implied from the necessity doctrine in the context of
patient care or in cases of research where the information is anonymised; (2) court
order in personal injuries litigation; (3) where disclosure if in the person’s best
interests; (4) where disclosure is in the public interest (e.g. infectious disease
control); (5) where disclosure is necessary to protect another specific individual –
arguably protection of another affected relative would be covered by this exception,
whether or not a cure is available for the disease. This, of course, raises difficulties
with regard to the right not to know. It may also be argued in this context that the
17
Advisory Committee on Genetic Testing, Advice to Research Ethics Committees (London: October
1998), p. 6
12
information is not owned by the person tested but by the family sharing the same
gene pool.
xi.
Governments, the criminal justice system, employers and insurers should not be
authorized to compel patients to provide samples which would disclose genetic
traits or disorders, unless in the interest of public health.
xii.
Unless specific disease intervention or prophylaxis is available, children should not
normally undergo predictive genetic testing until they have reached the age of
consent and so are able to request the test on their own behalf.
12.
Research participants have a right to know individual research results that
affect their interests, but should be able to choose whether to exercise that right.
Researchers must decide at the beginning of a project what information about
the results of laboratory tests done on samples should be available to the
participants, and agree these plans with the Research Ethics Committee. If
research results have immediate clinical relevance, there is a clear duty of care
to ensure the participant is informed.18

Where research groups are dealing with non-anonymised samples important
ethical issues will arise with regard to feedback to individual patients and families.
These should be addressed in collaboration with a recognized clinical genetics
unit.

Tests done on samples of human material in the course of research may reveal
information that has implications for the donors’ future health or healthcare, or
otherwise impacts on their interests. It is important to decide before the start of a
research project what will be done if this arises. Researchers should be cautious
about assuming that they, rather than the individuals concerned, are best placed to
judge what information is of interest to donors on a case-by-case basis. For
instance, some researchers may take the view that information should only be fed
back if there is a treatment or preventive intervention available. However, research
participants might wish to know predictive information about their future health,
even if there is no treatment available, for example to take it into account when
making important life decisions, such as whether to have children. Researchers
should assume that participants have a right to know information that may affect
their interests, but that they might choose not to exercise that right. When
participants are asked to make a decision on whether or not they want results to be
fed back to them they must be given sufficient information to allow them to decide
what their interests are and to make any refusal meaningful. Researchers must
decide at the outset what their strategy will be with regard to feeding back
information and whether any linkage of research results to individuals will be
possible or alternatively whether the unlinked anonymous technique is appropriate.
This must be set out in their submission to the Research Ethics Committee, and the
policy adopted must be explained clearly to research participants before they
consent to take part in the research.
18
Medical Research Council, Human and biological samples for use in research: Operational and
Ethical Guidelines (London: 2000), p. 4.
13

Research results obtained on anonymised unlinked samples cannot have any
impact on the interests of an individual donor, and cannot be fed back. Much
research can be done using anonymised unlinked samples, and indeed in many
instances this is the most appropriate technique.

However, irreversibly breaking the link between a sample and the individual donor
can undoubtedly reduce its value for some types of research, for instance by
making it impossible to add follow-up data or to audit fully the research results. In
deciding whether to use anonymised unlinked samples, researchers should take
into account the nature of the foreseeable research findings, the importance of
obtaining follow-up information on participants, the initial consent obtained and
the feasibility of obtaining further consent. The ability to provide feedback linked
to counselling and clinical care must also be considered. There are various
possible strategies for unlinking: samples can be irreversibly unlinked from the
outset, or they can be unlinked after the initial study is done, either before being
used for any secondary studies or before use in specific studies only.

It should be ascertained at the approval stage whether the pharmaceutical company
plans to contact the patient and/or his/her family if information is acquired during
the test which may have a detrimental affect on the patient's future health or that of
his/her family.
This is only possible for samples that are not anonymised. Pharmaceutical
companies do not usually have any direct knowledge of the identities of patients in
clinical trials and do not normally ever make direct contact with patients.
Incidental clinical findings

Incidental genetic information should be divulged to the patient only in
circumstances where failure to do so would create a significant risk to their
health or to the health of their offspring. This should occur associated with
appropriate genetic counselling.

Where a result that can be linked to an individual has immediate clinical
relevance (for example, if it reveals a serious condition for which treatment is
required), the clinician involved has a clear duty of care to inform the
research participant, either directly or via the clinician responsible for his or
her care. The clinician responsible for care should always be notified, and
participants should be informed that this will occur. A research result should
not be relied on as the sole basis for diagnosis, since quality control standards
in research laboratories generally differ from those used for clinical testing.
Research participants or their clinicians should be advised to seek a repeat or
confirmatory test by a clinical diagnostic laboratory where possible.
Research results

In the context of unlinked research results, it might often be worthwhile for
general results to be made available to subjects and their doctors so that
participants have the choice to seek counselling and further testing to
ascertain their individual status vis-à-vis a particular result.
14

There is a certain moral obligation on researchers regarding results of genetic
research disclosing an abnormality affecting the health of the research
participant. It may be appropriate that the researchers indicate to the
participants that further diagnostic tests be done. The option should, in any
case, be given to the participants in the study as to whether they wish to
receive specific results or not, either during or at the end of the study, or
indeed into the future. It is recommended that when it is proposed to disclose
results to research participants there should be an established procedure.

There is currently no consensus on whether, or under what circumstances, it
is appropriate to feed back research results to participants on an individual
basis. Often the clinical relevance or predictive value of a research result is
unclear, at least initially, and there will be no individual data of value to be
fed back. It will always be difficult to define the point at which a research
hypothesis becomes a clinical fact. Where consent is being sought for a
specific research project at the time a sample is collected, the potential
relevance, if any, of the results for the participant should be explained and the
opportunity to receive feedback of individual results should be offered where
appropriate. There should be a mechanism in place for participants to change
their minds (for instance, a contact telephone number). If feedback is
requested, they should be given appropriate instructions about how to notify
researchers of a change in their address. Researchers feeding back individual
results must be prepared to explain their significance to the participant and to
advise on access to counselling or treatment where indicated.

It is good practice to offer research participants the opportunity to be kept
informed about the general results of research projects done using the
samples they have donated, though this may not be appropriate in all
circumstances. Participants could be informed by posting information on
research outcomes on a website, or by offering them the opportunity to
receive a newsletter. Where the clinical relevance of research results becomes
clear some time after the sample was obtained, or where the results obtained
from secondary research may impact on the donors’ interests, these routes
should be used to inform donors that results of potential interest may be
available and offer them the opportunity to receive individual feedback or
advice if they wish. Similarly, when new predictive tests of clinical value
become available as a result of the research, participants can be informed how
to access these tests if they wish.

Where samples may subsequently be used for secondary studies, a
mechanism should be put in place to allow participants the opportunity to
seek individual results that might impact on their interests. It is acceptable for
the onus to be on the participant to seek the information rather than on the
researcher to be pro-active in providing it. The research protocols for
secondary studies and the arrangements (if any) for feeding back results to
participants must be reviewed by a Research Ethics Committee, preferably
the committee that oversaw the making of the collection. If samples from a
collection are shared with other researchers, the custodian of the collection is
15
responsible for all contacts with donors, including providing any information
on research results with a possible impact on individuals.
13.
Specific issues related genetic research
i.
Much genetic information obtained for research purposes is of unknown or
uncertain predictive value. Genetic tests of known clinical or predictive value
should not be done on samples that can be linked to an individual without their
specific consent, and appropriate counselling should be available if consent for such
a test is sought. Participants should be advised of the possible implications of
genetic information for other family members and the potential impact on family
relationships, and also of the implications of genetic risk information for
employment or their ability to obtain insurance, before they decide whether to give
consent to the test or whether they want to know the result. The feeding back of
other genetic information, the significance of which is currently unknown could
also have similar implications in the future.
ii.
Genetic information is particularly sensitive. The considerations that support the
(not controversial) view that genetic information is different from other medical
information have included the fact that we share genetic information with relatives
and that it is not specific to time. This gives such information a predictive aspect,
for both individual patients and their relatives, which in turn makes the dangers
arising out of disclosure particularly acute, because of the possibility of adversely
affecting the future course of someone's life. Some have argued for a right not to
know such information. While all these features may be true to a greater or lesser
degree of other medical information, what does seem to be the case is that these
features give rise to different possible interpretations and implications, which may
make more likely the unintentional inflicting of harm?
iii.
Patients have the right to control the use of all medical information about them,
including genetic information.19 The predictive or risk assessing nature of genetic
information makes it valuable to heath care planners, insurers, and people
evaluating long-term concerns such as education, carer choices, and risk avoidance
and health promotion.20 The possibility of insurance discrimination has made the
confidentiality of genetic information even more important.21 Doctors should
ensure that patients understand that after genetic testing their ability to qualify for
insurance may be affected. Even though including in clinical records the results of
genetic testing conducted in the course of research is not always appropriate,22 the
legal definition of 'health care record' includes all written information about a
19
I. Kleinman, F. Baylis, S. Rogers, P. Singer, "Bioethics for clinicians: 8. Confidentiality", CMAJ
156(1997): 521-4.
20 T. Lemmens, "What about your genes?" Ethical, legal and policy dimensions of genetics in the
workplace. Politics Life Sci 16(1)(1997): 57-75.
21 T. Lemmens, P. Bahamin, "Genetics in life, disability and additional health insurance in Canada: a
legal and ethical analysis", Report to Medical, Ethical, Legal and Social Issues Advisory Committee of
Canadian Genome Analysis and Technology Programme, November 1996; NIH-DOE Working Group
on Ethical, Legal, and Social Implications of Human Genome Research. Generic information and
health insurance. Report of the Task Force. Bethesda (MD): National Institutes of Health, 1993.
22 K. Glass, C. Weijer, T. Lemmens, R. Palmour, S. Shapiro, "Structuring the review of human genetic
protocols. Part II: diagnostic and screening studies", IRB: Rev Hum Subj Res 19(3.4)(1997): 111,13.
16
patient. Separate records provide little protection to the patient and may
compromise care if the genetic information is such that it would affect treatment in
the future or be of interest to a family member. Departments of medical genetics do
maintain familial records that link the genetic records of individual patients to assist
with the clinical services they provide. Nevertheless, information from these
records is typically shared with family members only with the consent of the person
whose test results are being disclosed. The familial nature of genetic information
can create a conflict for the doctor, who has a duty to maintain confidentiality but
may feel a duty to warn family members of possible risk. Ultimately, the issues of
duty to warn and access to health care records will probably be decided by
legislation.
iv.
Respect for the person and for the family can be facilitated and ensured by avoiding
the use or transmission of identifiable samples wherever possible. Data protection
is of the utmost importance. The coding of samples is a technique that protects
confidentiality provided that stringent mechanisms are put in place. Another
avenue is the anonymization of samples, which would make tracing back
impossible. While necessary demographic and clinical data may accompany the
anonymised sample, careful consideration should be given before proceeding to
strip samples of identifiers since other unknown, future uses may thereby be
precluded as well as may the validation of results.
v.
The family is the nexus of a variety of relationships (legal, moral, social and
biological). Irrespective of legal definitions of the family and of its different social
and cultural configurations, genetic research may yield genetic information that is
important to immediate relatives. The very fact of participation in research or not,
or, the decision to refuse to warn at-risk relatives or to withdraw, or, the failure to
provide for access after death, all affect the interests of present and future relatives.
vi.
These shared biological risks create special interests and moral obligations with
respect to access, storage and destruction that may occasionally outweigh individual
wishes. A different response is necessary however, in relation to institutional third
parties, such as employers, insurers, schools, and government agencies because of
possible discrimination. Counselling prior to participation is also necessary to
avoid stigmatisation. Standardisation of procedures and the security of the samples
are essential.
vii.
Security mechanisms must be put into place to ensure the respect of the choices
made and of the desired level of confidentiality.
viii.
While an ethical case can be made for the access to stored DNA of a person by
immediate relatives the general view is that without the explicit consent of the
person access cannot be given even where there is specific treatment for a disease,
which might flow from that information. A person cannot access their relative’s
information, without the prior consent of the person who’s DNA it is. This
confidentiality extends beyond the death of the person involved.
ix.
In the absence of need for access by immediate relatives, stored samples may be
destroyed at the specific request of the person. Such destruction is not possible for
samples already provided to other researchers or if already entered into a research
17
protocol or used for diagnostic purposes. By their very nature, anonymized samples
cannot be withdrawn or destroyed.
x.
Unless authorised by law, there should be no disclosure to institutional third parties
of participation in research, nor of research results identifying individuals or
families. Like other medical information, there should be no disclosure of genetic
information without appropriate consent.23
Multiple genetic testing24

Does the research protocol involve the use of technologies that permit multiple genetic
tests to be performed?
Research involving multiple gene tests is no different from that where the research
protocol involves a single gene test.
Studies such as those labelled as "genotyping" or "genetic profiling" which are being used
for drug development or in pharmacogenetics must be treated as genetic testing. The
fundamental issues of information, consent, and confidentiality are unaltered. The
challenge for researchers is to establish suitable, "user friendly" methods by which
complex information about their research can be explained to participants.
Research involving "at risk" individuals and their families25

Does the research place unacceptable burdens on individuals from a family with a known
genetic disorder?
Where samples are to be taken from families with genetic disorders, it is important that
healthy individuals are not sampled unless strictly necessary. There is often a tendency for
researchers to view "healthy" members of a family as patients and this risks unnecessary
"medicalisation" of these individuals. Where unaffected subjects are to be included in a
study this must be carefully justified and there must be a clear plan as to what would be
done in the event of an abnormality being identified. Caution needs to be applied so that
families with a known genetic disorder are not overwhelmed by approaches to participate
in research projects.
14.
A copy of the Pharmaceutical Company’s code of ethics and protocol should
accompany all research protocols. The Pharmaceutical Company applying for
research approval should also demonstrate how Quality Control will be
monitored, i.e. the laboratory should be accredited by a recognized
international agency.
All equipment and reagents for testing should be manufactured and maintained to an
appropriate level and provide assured levels of accuracy and reliability that reflects
current best practice.
All laboratories offering genetic testing services should be appropriately staffed and
equipped, and should:
23
HUGO Ethics Committee Statement, op. cit., pp 56-57.
Advisory Committee on Genetic Testing, Advice to Research Ethics Committees (London: October
1998), p. 8
25 Advisory Committee on Genetic Testing, Advice to Research Ethics Committees (London: October
1998), p. 8
24
18
a. Participate in an appropriate accreditation scheme;
b. Join an appropriate external quality assurance scheme; and
c. Perform adequate internal quality control.
All such systems should reflect current best practice.26
15.
The contracting laboratory needs to clarify the disposition of samples at the end
of the contract period, if the laboratory ceases operations, if storage fees are
unpaid, or after a death or divorce.
16.
The Pharmaceutical Company needs to clarify how it intends to deal with the
consequences of unauthorised release, loss or accidental destruction of samples.
17.
The Pharmaceutical Company will need to clarify what steps it has put in place
to ensure the availability of genetic counselling for the patients.
18.
Transmission of Genetic Information outside the EU

Genetic Information should only be transmitted outside the EU to jurisdictions
with legal safeguards to protect confidentiality that are equivalent to those
currently applied in the EU

Any medical information to be stored within Ireland is subject to the Data
Protection Act 1988, the Freedom of Information Act 1997, and the EC
Directive on the Protection of Data: 95/46/EC. These Acts and the common
law ensure that third parties do not have access to information save with the
consent of the individuals to whom the information pertains.27

Directive 95/46/EC on the Protection of Individuals with regard to the
Processing of Personal Data and on the Free Movement of Such Data.
The Irish Acts protect information within Ireland. The new Directive aims to
ensure that information that is conveyed to non-EC countries or ‘third
countries’ is done so only when such a country also has satisfactory legislation
or practices in place that will ensure data protection. Where this is not the
case, the information, in the normal course of events, cannot be transferred.28
Further to the obligations of the Directive, its implications are that: (i) the
relevant third country has legislation or practices in place that adequately
protect personal data or (ii) assurances need to be gained by a ‘third country’
that the data received will be protected, or when ‘third country’ protection is
not adequate then the data can be transferred only if (iii) the data subject gives
his/her consent unambiguously to transfer the data.29
26
Advisory Committee on Genetic Testing, Code of Practice and Guidance on Human Genetic testing
Services Supplied Direct to the Public (London: Health Departments of the United Kingdom,
September 1997), p. 8
27 For other exceptions to the law please refer to the legislation.
28 A. Sheikh, Genetic Research and Human Biological Samples: The Legal and Ethical
Considerations, (Dublin: Health Research Board, 2002), pp 51.
29 A. Sheikh, Genetic Research and Human Biological Samples: The Legal and Ethical
Considerations, (Dublin: Health Research Board, 2002), pp 54.
19
In light of the uncertainty, it is advisable where ‘third countries’ are involved
in joint research projects that a written assurance be given to the EU-member
country stating that the absolute privacy of data subjects is protected and that
any third party not a part of the research team will not have access to the
information and samples and that the information and samples will be secured.
This written assurance should be both explained to potential research
participants and either shown to them or available for inspection.30
It is only in the case of anonymous or anonymised samples that the provisions
of the Directive would not apply, since they would be unidentifiable and would
therefore not come within the ambit of the definition of ‘personal data’.31
In circumstances where there exists any doubt, the Data Protection
Commissioner can also be contacted.
30
A. Sheikh, Genetic Research and Human Biological Samples: The Legal and Ethical
Considerations, (Dublin: Health Research Board, 2002), pp 55.
31 A. Sheikh, Genetic Research and Human Biological Samples: The Legal and Ethical
Considerations, (Dublin: Health Research Board, 2002), pp 57.
20
APPENDIX 1
Commentary on No. 6
Informed consent is required from the donor (or the next of kin, if the donor has died)
whenever a new sample is taken wholly or partly for use in research.
i.
When obtaining consent to take a sample of biological material for research, it is
important that donors have sufficient understanding not only of the process
involved in obtaining the sample and any associated physical risks, but also of what
the sample is to be used for and how the results of the research might impact on
their interests. Written evidence of consent must normally be obtained. Written
consent is not a substitute for careful explanation. It is simply a means of providing
documentary evidence that an explanation of the research has been provided and
consent has been sought. Signed consent forms and/or any other documentary
evidence of consent, together with copies of patient information materials, must
always be kept for future reference. If the information leaflets are revised in the
course of a study, all the new versions must be numbered and kept and details of
when the changes were introduced should be recorded.
ii.
If research using samples will require the collection of information from the donor’s
medical records, then consent must be obtained from the donor. It must be clear
who will access the records, what information will be obtained, and how the
patient’s confidentiality will be protected.
iii.
When seeking consent for research, information for potential participants must be
presented in a form that can be understood by participants.
iv.
Obtaining informed consent to genetic testing is particularly challenging in view of
the complexity of genetic information, the controversial nature of clinical options
such as abortion or prophylactic surgery of unknown efficacy, and the social and
psychological implications of testing.32 Positive genetic test results are rarely
accompanied by the prospect of either treatment or cure. In the absence of effective
treatment, the potential for psychological harm and social discrimination must be
considered. Patients must evaluate whether the benefit of testing is worth the risk.
When genetic testing is part of research, the purpose of the research should be made
clear to the patient and uncertainties that might arise as a result of testing
discussed.33
v.
Another area of concern is that the possibility of being 'informed' in this area relates
to the idea that it is simply not possible to be genuinely informed of all the risks and
benefits involved. The idea behind this concern is that no-one can be completely
informed, because it is not possible to foresee the range of uses to which genetic
information about someone might be put. The legal and ethical regulation of this
area is still developing, so that individuals are making choices in an uncertain
32
E. Etchells, G. Sharp, P. Walsh, J. Williams and P. Singer, "Bioethics for clinicians: 1. Consent",
CMAJ 155(1996): 177-80; E. Etchells, G. Sharp, M. Burgess, P. Singer, "Bioethics for clinicians: 2.
Disclosure", CMAJ 155(1996): 387-91.
33 C. Weijer, B. Dickens, E. Meslin, "Bioethics for clinicians: 10. Research ethics", CMAJ 155(1996):
1153-7.
21
situation. Discrimination, in particular, is a live issue relevant to the consent
process. It is to a large extent because of the potential for stigmatisation and
discrimination, e.g. from insurers and employers, that the informed consent issues
involved in genetics have been so concerned with privacy and confidentiality. This
information may be disadvantageous (as well as having potential advantages to
people seeking information facilitating their own health-related decisions) to
members of an identifiable group as well.34
Researchers have an obligation to ensure
researcher/doctor and patient/sample donor.
vi.
confidentiality
as
between
The choices offered in the consent process should reflect the potential uses of the
DNA sample and its information. It is important to indicate whether the sample and
its information will: identify the person, code the identity, or anonymise the
identity so that the person cannot be traced although some demographic and clinical
data may be provided.
Even if anonymization is appropriate in certain
circumstances in research, caution should be exercised in any irreversible stripping
of identifiers from the samples since it may preclude valuable uses of the samples
and validation of results.
Anonymisation is appropriate for certain types of study (e.g. general studies on a
disease) and in fact gets around some of the ethical issues of genetic testing during
clinical trials. For this reason, samples of genetic material collected during clinical
trials are regularly anonymised. It is noteworthy that in any case, the IMB requires
stored samples to be anonymised within five years of completion of a clinical trial.
vii.
A potentially worrying feature of genetic information is the way in which it is
perceived as intricately bound up with our identities as persons. It has been
suggested that DNA is the modern secular equivalent of the soul, or at any rate the
guarantor in some sense of who we are. However well grounded this view may be,
in this respect the information takes on a new significance which may affect the
nature of informed consent. This is because people are not just taking decisions
about allowing the use of some piece of medical information which is incidental to
their identity; they are making choices about what may appear to them to be in a
deep sense part of themselves. The sensitivity of genetic information thus resides
not only in the harms that may ensue from its use, but also from a perception of its
association with what is most intimate and personal. This suggests the need at least
for special care in the informing process.35
Particular considerations apply in the case of research involving children and people
who, as a result of permanent or temporary mental incapacity, cannot give valid
consent. Safeguards must be in place to ensure that the autonomy of such patients is
protected.
viii.
Research subjects should be given adequate time to absorb the information
provided, before a decision is taken to be tested or a result is given.
R. Chadwick, “Bioethics and Medical Practice in the Age of Molecular Genetics”, Biomedical Ethics
5(2000): 9.
35 R. Chadwick, op. cit. pp 11-12.
34
22
In genetics clinics, a two-step approach has been found to be important in allowing
time for reflection. Since a premium is often placed on avoiding delay in other
laboratory testing situations, it is important that this time interval is protected.36
The Control of Clinical Trials Act 1987 requires patients to have six days to consider
the information about a clinical trial before the trial can commence.
ix.
If sample anonymisation takes place, this should be clarified to the subject, and they
should be informed that no individual results will then be fed back.
Recommendations

Informed consent is a continuum or process. Participants need to be informed at
various stages of what are occurring and their consent sought if new tests are to be
initiated.
However, it may prove impractical to have to go back to the patient for consent for
each future new type of test and the consent form should be worded so as to
provide permission to carry out other tests in the future). In any case, it is not
possible to revert to the patient if new tests are to be carried out on anonymised
samples.

Ongoing research on the issue of informed consent with regard to genetic testing is
of paramount importance.

It is evident that more effort needs to be put into the informing process. This
implies that the doctors obtaining patient consent are familiar with the implications
of genetic testing. Surveys done of consultants and General Practitioners
demonstrate that large percentages are not familiar with the various implications of
genetic testing. Another important element is access is genetic counselling. The
availability of genetic counselling is frequently cited as a criterion for the ethically
acceptable introduction of genetic screening programmes. The problems of
resourcing the growing demand for counselling, however, have not been
satisfactorily resolved.
36
Advisory Committee on Genetic Testing, Advice to Research Ethics Committees (London: October
1998), p. 7
23
APPENDIX 2
TERMS
Anonymised samples or data have had any identifying information removed, such that it is
not possible for the researcher using them to identify the individual to whom they relate. The
term is used in these guidelines to refer to both linked and unlinked anonymised data and
samples.
• Linked anonymised samples or data are fully anonymous to the people who receive or use
them (e.g. the research team) but contain information or codes that would allow others (e.g.
the clinical team who collected them or an independent body entrusted with safe-keeping of
the code) to link them back to identifiable individuals.
• Unlinked anonymised samples or data contain no information that could reasonably be used
by anyone to identify the individuals who donated them or to whom they relate.
Coded samples: or data have a coded identification to protect the confidentiality of the
individual during routine use, but it is possible for the user to break the code and thus identify
the individual from whom they were obtained.
Custodianship: Responsibility for safe keeping of samples and control of their use and
eventual disposal in accordance with the terms of the consent given by the donor.
Custodianship implies some rights to decide
how the samples are used and by whom, and also responsibility for safeguarding the interests
of the donors.
Existing collections: collections comprising samples that were collected and stored before
these guidelines came into operation.
Genetic research: Investigation of variation in the nuclear or mitochondrial DNA that forms
the genome of an individual and may be inherited from parent to child. This may involve
direct analysis of DNA or analysis of
Gene products.
Genetic testing: Tests to detect the presence or absence of, or alteration in, a particular gene,
chromosome or gene product, in order to provide diagnostic or predictive information in
relation to a genetic disorder. (Such testing does not necessarily require the use of genetic
technology.)
(a) Diagnostic Genetic Testing - Use of genetic testing in a symptomatic individual to aid in
their diagnosis, treatment and management.
(b) Presymptomatic Genetic Testing - primarily carried out in healthy or asymptomatic
individuals to provide information about that individual's future health, with respect to
specific inherited diseases. Such a test result may indicate that the individual has a high
likelihood of developing the disorder or of excluding it. Presymptomatic testing is most
frequently used in late onset autosomal dominant disorders such as Huntington's Disease.
(c) Susceptibility Testing - which provides information about the genetic component in a
multifactorial disorder
24
(d) Carrier Testing - used to detect individuals who possess a single copy of a gene which
follows an autosomal recessive pattern of inheritance (see below). Such an individual will not
normally develop any disease or disorder but may pass on the gene to his or her offspring.
Carrier testing can also be done for X-linked and chromosomally inherited conditions, as well
as for autosomal recessive conditions.
Multifactorial
Disorders whose genetic components are not the sole cause, but which work with other often
environmental factors in determining a disease outcome. Multifactorial disorders include
many cardiovascular diseases, most Alzheimer's Disease of old age and some forms of
diabetes.
Autosomal Recessive Disorders
Disorders, where for a person to be affected, a mutation has to be inherited from both parents.
Such parents are usually unaffected carriers because they only have a single copy of the
mutant gene. Recessive disorders commonly have onset in childhood and include cystic
fibrosis, sickle cell disease and thalassaemia.37
(e) Molecular genetic tests
Molecular genetic tests have a predictive and immutable quality, which is not necessarily the
case for many other tests carried out as part of a research project.
Human material: All biological material of human origin, including organs, tissues, bodily
fluids, teeth, hair and nails, and substances extracted from such material such as DNA or
RNA.
Human tissue or sample collection: Any samples of human biological material to be kept
for reference, teaching or future research use.
Pharmacogenetics/pharmacogenomics: Profiles of genes involved in drug metabolism are
quite distinct from those involved in disease. Pharmacogenetics/pharmacogenomics has the
potential to affect the way drugs are prescribed in the future with identification of new and
potentially disease-modifying drug targets, however it may also allow gain or benefit to
accrue to the individual participating in such a clinical trial. For such an individual
knowledge gained from study participation may allow a better understanding of his or her
individual variation in response to pharmacotherapy i.e. by correlation of SNP/haplotypes
with response to therapy it may be determined whether this individual is likely to respond to a
medicine and to not experience side effects from it.
The context of a genetic test needs to be clearly stated. If a sample is being analysed on a
research basis, then no direct result should be given to the patient. A separate accredited
diagnostic molecular genetic laboratory should reproduce clinically important results, before
any clinical actions are taken. If genetic results are being given, then genetic counselling by
trained personnel should be available for the family consequences of such a test.
Personal information: all information about individuals, living or dead. This includes
written and electronic records and information obtained from samples.
37
Advisory Committee on Genetic Testing, Advice to Research Ethics Committees (London: October
1998), p. 3.
25
Types of Research38
There are two main categories of medical research: Therapeutic and Non-therapeutic.
Therapeutic Research
The primary aim of therapeutic research is essentially diagnostic, that is, to diagnose and/or
cure a disease or illness. The research participant will usually be a patient, in other words,
he/she will actually receive treatment, albeit new or experimental, which it is hoped will have
a therapeutic benefit on the patient/research participant. The desired benefit is therefore direct
in terms of treatment.
Non-therapeutic Research
The primary aim of non-therapeutic research is not immediate therapy but, through testing a
hypothesis or through the collection of data, a contribution to general knowledge is made or a
discovery of knowledge is made. Thus, although the research may benefit the subject in the
future or in the longer term, it is not directed intentionally as therapy to the subject
The main and simplest distinction between the two types of research, therefore, lies in the aim
of the researcher.
In therapeutic research, there exists the dual intention and aim of:
i.
Seeking to benefit the patient who is the research subject by means of treatment,
and
ii.
Gathering data of a generalised/specific nature.
In non-therapeutic research, the primary intention is that of gathering data and increasing
knowledge and not immediate treatment.
Thus research which seeks to identify the genetic basis of disease by collecting
biological/bodily/DNA samples from research participants is non-therapeutic. The collection
of such samples may identify the genetic basis of the disease by locating the gene/s possibly
responsible for certain conditions and diseases and may offer the benefit of insights into the
disease, but such research will not usually offer the present and direct benefit of treatment.
Those benefits are in the long term.
38
A. Sheikh, Genetic Research and Human Biological Samples: The Legal and Ethical
Considerations. (Dublin: Health Research Board), 2002, pp 25-27.
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APPENDIX 3
Checklist for research based on samples of human material.
Source of samples

If new samples are to be collected for this research, will appropriate measures
be taken to minimise any risks of physical harm. Could the approach to
potential donors cause distress?

If samples are to be collected from patients temporarily unable to give consent
(e.g. during emergency surgery), are there appropriate arrangements to consult
next of kin, to obtain informed consent later and for patients to opt out if they
wish.

If the research is using samples originally collected for another research
project, is the research covered by the consent already obtained? If not, can
new consent be obtained from the donors or can the samples be anonymised
and unlinked?

If the research will use material surplus to clinical requirements, are the
patients aware that their material might be used in this way and of their right to
object? Would it be practicable to obtain individual consent?

If samples are to be obtained after death, is it possible to discuss the study with
potential donors and obtain consent before death? If not, are appropriate
arrangements in place to get consent from the next of kin?
Justification for the study

Could information obtained in the course of the research bring harm or distress
to the donors, individually or as a group, or to members of their family?

Do the potential benefits of the research outweigh the risks?
Conduct of the research



Are adequate measures in place to protect the confidentiality of personal
information required for or revealed by the research?
Is it clear to donors who will have access to their samples or personal
information about them?
What will happen to the samples after the research is finished? Will
appropriate consent be obtained if they will be stored for future use?
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Feedback of information



Could tests done on the samples as part of the research reveal information of
immediate relevance to a donor’s health or healthcare? If so, will the donors be
made aware of this possibility and are the arrangements for feeding back this
information appropriate? Have the arrangements been agreed with the people
responsible for the donors’ clinical care?
Could tests done on the samples as part of the research reveal predictive or
other information that might affect the interests of the donor or their family? If
so, are arrangements in place to make that information available to donors, and
will they have adequate information to make a decision as to whether they
want the information? Would it be better if the samples were anonymised and
unlinked before testing?
Is it clear to participants where they can get information about the outcome of
the research?
Points of Concern39
1.
Non-therapeutic research must have the objective of the ultimate attainment of some
benefit to participants – it cannot be merely an exercise of ‘a wish to obtain
knowledge’. Such rationale is based on the general reasoning that non-therapeutic
research has no ‘benefit’ to a research participant. While this may be accurate in
terms of direct benefit in relation to treatment, to say that non-therapeutic research
holds no ‘benefit’ at all to the participant is not entirely accurate. This is especially so
in relation to research into the genetic basis of disease, since the findings of such
research, while not immediately aimed at treatment, therapy or cure, may give
invaluable insights into diseases which my hold indirect benefits to research
participants.
In the case of the competent adult, in cases of both therapeutic and non-therapeutic
research, once there is full disclosure of all facts (in relation to the objectives of the
research, the personnel involved, the procedure involved, existence of alternatives, the
side-effects if any and risks, advantages and disadvantages) to the adult, it will be the
adult who will consent by means of a written informed consent.
2.
The questions must be asked:
 Will participants be competent to give consent?
 If not, what safeguards are in place to ensure the protection of their dignity and
autonomy?
3.
Have the full extent and ramifications of the research been conveyed to the potential
participants or those consenting on their behalf, and how has this been done?
4.
It is recommended that research participants should be provided with a proper and full
but comprehensible information pack/leaflet; the pack could possibly contain pictorial
diagrams to explain the basics of genetics, the research in its various steps and the
medical benefits, whatever they may be, that will or may result to the participant.
39
A. Sheikh, Genetic Research and Human Biological Samples: The Legal and Ethical
Considerations. (Dublin: Health Research Board, 2002), pp 61-62
28
5.
It is recommended that a presentation involving visual aids could be given to
participants by the research/medical team.
6.
Individual sessions with participants should also be held.
7.
Will participants receive feedback or results directly or at all?
8.
If, so will genetic counselling be provided?
9.
If not, are there mechanisms in place, such as the posting of leaflets or a website
whereby participants can follow the progress of the research if they so wish.
10.
Are confidentiality agreements in place?
11.
The research proposal entailing genetic research must have independent ethical
committee approval.
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APPENDIX 4
Guidance on the production of a patient information leaflet
This indicates general issues that must be covered for all research studies. In addition, the
following specific issues should be covered in the process of obtaining informed consent and
in the patient information leaflet for studies in which samples of biological material will be
taken from participants. Information leaflets should always meet basic criteria for good
quality information provision.
1. For all samples









2.
The sample will be treated as a gift.
The donor has no right to a share of any profits that might arise from research
using the sample.
Who will be responsible for custodianship of the sample (host institution/funding
body).
What personal information will be used in the research.
The arrangements for protecting the donor’s confidentiality.
Arrangements for feeding back or obtaining access to individual research results, if
any, and for informing participants of the outcome of the research.
Consent to access medical records, if required.
Specific consent for any genetic tests, if required.
The donor needs to be informed whether the sample will be anonymised or not,
and if so, that no individual results will then follow for the patient.
If the sample is to be stored for possible secondary use






The types of studies the sample may be used for and the diseases that may be
investigated.
Possible impact of secondary studies on the interests of donors and their relatives.
Means of accessing information on secondary studies, if appropriate.
Secondary studies will have to be approved by a Research Ethics Committee.
Consent to share samples with other users.
Consent to commercial use, and an explanation of the potential benefits of
commercial involvement, if appropriate.
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