Contents
Page
Introduction
2
Principles
2–4
Appendix 1: Terms
5–7
Appendix 2: Checklist - Samples of Human Material
8 – 10
Appendix 3: Guide for production of Patient Information Leaflet
11
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, 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
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.
5.
The human body and its parts shall not, as such, give rise to financial gain.
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.3
7.
Information on Genetic Testing for Participants in Research:
Requirements.4
i.
Information
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?
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.
4 Advisory Committee on Genetic Testing, Advice to Research Ethics Committees (London: October
1998), p. 9
2
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.
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.
9.
There should be a clear separation of the research specimen from service testing
samples.
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.
3
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.5
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.6
13.
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.
14.
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.
15.
The Pharmaceutical Company needs to clarify how it intends to deal with the
consequences of unauthorised release, loss or accidental destruction of samples.
16.
The Pharmaceutical Company will need to clarify what steps it has put in place
to ensure the availability of genetic counselling for the patients.
17.
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
5
Medical Research Council, Human and biological samples for use in research: Operational and
Ethical Guidelines (London: 2000), p. 4.
6 Medical Research Council, Human and biological samples for use in research: Operational and
Ethical Guidelines (London: 2000), p. 4.
4
APPENDIX 1
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
5
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
(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.7
(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.
7
Advisory Committee on Genetic Testing, Advice to Research Ethics Committees (London: October
1998), p. 3.
6
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.
Types of Research8
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
8
A. Sheikh, Genetic Research and Human Biological Samples: The Legal and Ethical
Considerations. (Dublin: Health Research Board), 2002, pp 25-27.
7
disease, but such research will not usually offer the present and direct benefit of treatment.
Those benefits are in the long term.
8
APPENDIX 2
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?
9
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 Concern9
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
9
A. Sheikh, Genetic Research and Human Biological Samples: The Legal and Ethical
Considerations. (Dublin: Health Research Board, 2002), pp 61-62
10
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.
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.
11
APPENDIX 3
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









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.
2. 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.
12