Download ELAC (10-09) 2 1 HUMAN FERTILISATION AND

ELAC (10-09) 2
HUMAN FERTILISATION AND EMBRYOLOGY AUTHORITY
ETHICS & LAW ADVISORY COMMITTEE
Committee:
Ethics & Law Advisory Committee
Meeting Date:
20th October 2009
Agenda Item:
7
Paper Number:
ELAC (10-09) 2
Paper Title:
PGD with exclusion testing and non-disclosure
Author:
Joanne Anton, Policy Officer
For Information or
Decision?
Decision
Resource Implications:
None
Recommendation to the
Committee:
Members are asked to consider this paper and provide
recommendations to the Authority on:
the licensing of exclusion testing; and to recommend that
this method of testing is acceptable
the additional ethical issues pertaining to PGD with nondisclosure and recommend either:
(a) a licence condition prohibiting the practice; or
(b) strong guidance about the ethical considerations and
leave it to individual clinics to determine whether or not
disclosure should be made in particular cases.
1. Introduction
1.1
At the January 2009 meeting ELAC discussed a paper on the licensing
of preimplantation genetic diagnosis. As part of this discussion ELAC
was asked to consider the licensing of PGD with exclusion testing and
whether the procedure complies with the statutory requirements
contained in the Human Fertilisation and Embryology Act 1990 (as
amended by The 2008 Act). Due to a lack of time at the January 2009
meeting, the Chair asked the Secretariat to bring a further paper to the
Committee on this issue.
1.2
Although not discussed in the original paper, the Committee is also
asked to discuss the licensing of PGD with non-disclosure, which may
pose particular ethical issues for consideration by the Committee.
What is exclusion testing?
1.3
Exclusion testing is a preimplantation test available to couples, where
one partner has a particular risk of a disease such as early onset
Alzheimer’s or Huntington’s, but does not wish to know if they will
develop the disease. The test allows for these patients to have children
who are free from the condition, while avoiding the parent at genetic
risk finding out his or her own status.
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1.4
In these cases the centre will use exclusion testing to select embryos
which have not inherited chromosomal material from the ‘at risk’
partner'
s affected grandparent. Embryos found to have
inherited chromosomal material from the affected grandparent are
excluded as high risk and not suitable for implantation. As no direct
genetic test for the mutation is carried out, the genetic status of the ‘at
risk’ partner is not revealed to the patient or to the clinic staff. This
procedure is therefore distinctive from other forms of direct embryo
testing.
1.5
Determining the particular risk involved in exclusion testing may be
difficult as half of the couples who wish to use exclusion testing would
not carry the faulty gene and therefore all of the embryos created
would be unaffected (including those that are discarded). Of those
couples that were at risk, half of the embryos discarded would also be
unaffected.
The diagram below further illustrates exclusion testing though linkage
analysis:
* Diagram from the ‘Preimplantation Genetic Diagnosis Huntington disease exclusion testing
Supplementary leaflet’, publication by Guys Hospital.
1.6
A potential limitation of exclusion testing arises in cases where both
parents of the ‘at risk’ patient are deceased, in which case clinicians
may have no genetic information to accurately identity the
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chromosomal material from the affected grandparent. It may however
be possible to obtain DNA from previous blood samples obtained from
one of the parents. In cases where there is no DNA available,
exclusion testing could not be performed.
1.7
Very occasionally a potential problem occurs in cases where the
parents of the ‘at risk’ patient share one of the same genetic markers
i.e. the affected parent is AB and the unaffected parent is AD. A
resulting embryo could be AA and have DNA from either the affected or
unaffected grandparent. This is known as an ‘uninformative result’.
However, this scenario is not very common.
What is non-disclosure testing?
1.8
PGD with non-disclosure is similar to exclusion testing, in that patients
are unaware of whether they have inherited the condition from their
parent. However, unlike exclusion testing, the embryos are tested
directly for the specific genetic condition. The clinicians therefore will
find out whether the patient has inherited the condition.
1.9
Exclusion testing is often viewed as preferable to non-disclosure
testing because the genetic status of the patient is not known and
therefore there is no burden on the clinics to withhold this information
from the patients. Further ethical issues pertaining to PGD with nondisclosure will be discussed in section 5 of this paper.
2. Background
2.1
The HFEA has previously licensed exclusion testing for Huntington’s
disease and early onset Alzheimer’s disease. It was agreed that the
seriousness and significant risk requirements, as stated in the 7th Code
of Practice, were met, whilst also considering the views of the peer
reviews. Please see the following extract from a Licence Committee
meeting:
The Licence Committee considered the ethical issues of exclusion testing in
comparison to other forms of PGD.
The Committee agreed that if testing was carried out in a way that made the carrier
status of patients known to staff this would place an untenable burden on staff when
dealing with patients who choose not to be informed of their status. The Committee
accepted that healthy embryos may be excluded from transfer as the result of
exclusion testing, but drew a comparison with the exclusion of healthy embryos as a
result of sex selection to guard against the risk of passing on sex-linked conditions.
2.2
The HFEA has not previously licensed PGD with non-disclosure. The
HFEA has previously licensed PGD for Huntington’s disease but only in
cases where the patient has been aware of his/her carrier status.
2.3
The Committee may wish to note, however, that an application has
recently been received from a centre to perform PGD with non-
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disclosure for Huntington’s. The decision on this application will be
deferred until the decision of the Authority, currently scheduled for
December 2009.
3. Legal Issues
3.1
The Executive has sought legal advice on whether exclusion testing
and non-disclosure meet the requirements set out in the new embryo
testing clauses in the Act. Schedule 2, paragraph 1ZA(2) sets out the
purposes for which embryo testing (for treatment) may lawfully be
carried out:
“2) A licence under paragraph 1 [PGD] cannot authorise the testing of embryos for
the purpose mentioned in sub-paragraph (1) (a) unless the Authority is satisfied—
(a) in relation to the abnormality of which there is a particular risk, and
(b) in relation to any other abnormality for which testing is to be authorised under
subparagraph(1)(b), that there is a significant risk that a person with the abnormality
will have or develop a serious physical or mental disability, a serious illness or any
other serious medical condition”.
3.2
The advice from the internal legal department is that as the statutory
requirements refer to authorisation of testing for an abnormality, rather
than authorisation of method of that testing. In future, only the
abnormality should be placed on the Authority'
s approved list. So for
example, the abnormality for which the testing of embryos is authorised
should be “Huntington’s disease” rather than "Huntington’s disease
with non-disclosure".
3.3
This reflects the agreed approach taken by Authority to approve PGD
for conditions ‘in general’, in which the decision would be based on ‘the
nature of the disability, illness or medical condition which is likely to
result from that abnormality’ rather than the specific features of a
individual case. This decision was also informed by Counsel’s opinion
obtained by Authority on the correct interpretation of section 1ZA(1)(b).
4. Ethical Issues
The right not to know
4.1
The right of a patient not to know their genetic make up is a principle
which is increasingly recognised in international biomedical law1. This
right is also referred to in international legal guidelines, most notably in
Article 10.2 of the European Convention on Human Rights which states
that ‘Everyone is entitled to know any information collected by his or
her health. However, the wishes of individuals not to be so informed
shall be observed.’2 A patient’s right not to know is also referred to in
1
Journal of Medical Ethics 2004;30: 435
Journal of Medical Ethics 2004;30:p 436
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the 8th edition of the HFEA Code of Practice (11.21). The Code advises
that when donors register, they should indicate whether or not they
wish to be notified if the centre learns that they have a previously
unsuspected genetic disease or they are a carrier of a harmful inherited
condition.
4.2
This right not to know is becoming particularly important in the field of
genetics when more and more people are able to find out if they are at
risk from a medical condition when there is no real chance of reducing
that risk or obtaining effective treatment.
4.3
Many people in this situation choose not to have a genetic test,
preferring not to know their status. For example, the take-up rate of
pre-symptomatic testing for Huntington’s disease is only about 18% of
those who are at risk.3
The creation of unnecessary embryos
4.4
An additional ethical concern is the creation of embryos unnecessarily,
for those patients (or partners) who have not inherited the condition. In
these cases all of the embryos created would be unaffected. Also,
following exclusion testing all embryos which have inherited the
grandparent’s genes will be discarded, including those that do not have
the affected gene [this is not an issue for non-disclosure where only the
affected embryos are discarded]. An ethical tension therefore exists
between respecting the wishes of patients (i.e. to not undergo
predictive testing, whilst ensuring that any offspring are free of the
genetic condition in question) and unnecessarily discarding healthy
embryos.
4.5
However, exclusion testing has the same implications in terms of the
loss of embryos for replacement as PGD by means of sexing.4 PGD
with sexing also involves discarding potentially unaffected embryos to
avoid the risk of passing on a sex-linked condition. PGD with sex
selection for serious conditions has both been previously licensed by
the HFEA and enshrined in statute under the HFE Act 1990 (as
amended).
Unnecessary risks to patients
4.6
Another ethical concern is the risks associated with unnecessary
fertility treatment for half of the patients or their partners who have not
inherited the condition. These risks can include: reactions to fertility
drugs (including, ovarian hyper-stimulation syndrome), multiple births
and ectopic pregnancies. Both the clinician and patient will be unaware
of whether the risks associated with fertility treatment are indeed
necessary or not.
3
Genetic Testing Medical Ethics Today, The BMA’s handbook of ethics and law. Second Edition, p
322
4
Taskforce 5: preimplantation genetic diagnosis - report
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Consent to predictive testing
4.7
There may be pressure on a patient to give consent to predictive
testing, if exclusion testing/non-disclosure were prohibited. Patients
may feel unduly pressurised to be tested for the condition, if that was
the only method by which they could have PGD and ensure that any
offspring are free from the risk of inheriting the condition.
Case study- Guys Hospital
Guys Hospital has been carrying out PGD for Huntington’s disease since 2002.
Initially testing was only available to those who had undergone testing and were
mutation positive. However with the advances in preimplantation genetic haplotyping
in 2006, the centre began offering exclusion testing as well as direct testing, to those
couples where the partner with the HD family history was at 50% risk and had not
been tested. For these patients who were not aware of their genetic status and did
not want to find out, the centre decided only to offer exclusion testing and not PGD
with non-disclosure. The centre has carried out 9 cycles of exclusion testing.
The decision not to use non-disclosure PGD was based on the concern over
inadvertent disclosure of results in the embryos to the patients and the possible
negative psychological affects this may have; as well as the effect this knowledge
would have on all of the medical professionals involved with the patient. In addition,
the knowledge gained from carrying out PGD with non-disclosure would pose serious
ethical considerations for the medical professionals involved in cases where
unnecessary IVF treatment was being performed.
It was highlighted that there was considerable discussion amongst the Guys team
about offering exclusion testing. Some team members felt uncomfortable over the
issue of discarding healthy embryos and putting a woman through potentially risky
IVF treatment when it is not necessary. Although exclusion is offered, all Guy’s
patients are counselled about the problems associated with this. Some patients
decide after discussion to undertake predictive testing and then have direct PGD
testing.
However the centre considered it important that patients were not put under pressure
to undergo testing for a late onset disorder with no treatment, where the results of a
positive test could have major psychological and practical consequences.
5. PGD with non-disclosure - additional ethical considerations
5.1
PGD with non-disclosure as a method of testing presents a number of
additional practical and ethical problems due to the difficulty of
withholding the test results from the patients and the changes in
practice which may be required to avoid inadvertent disclosure.
5.2
Performing unnecessary medical treatment (with the associated risks)
would pose further ethical problems and conflict with a clinician’s duty
to make the care of a patient their first concern, as outlined in the
General Medical Council’s ‘Good Medical Practice’ (2006).
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5.3
This consideration may be counter balanced against the argument that
such treatment would always be necessary to protect the ‘at risk’
patient (or partner’s) right not to know their genetic status and their
right not to be forced into having predictive testing.
Burden on practioners
5.4
Non-disclosure involves directly testing embryos for a condition,
resulting in clinicians becoming aware of the genetic status of the
patient. Clinic staff would have to deal with the burden of this
knowledge whilst treating the patients. In addition the patient will be
aware that the professionals involved in their care will be withholding
this information from them.
5.5
A tension may exist for clinicians between respecting non-disclosure
and their own duty of care that a clinician should do no harm. For
example, if a clinician became aware during treatment that neither
partner was likely to develop Huntington’s i.e. all embryos were
unaffected, then when the patient returned for another IVF cycle, it
would be unnecessary to carry out fertility treatment with PGD and all
the risks attached. This may have associated problems and affect a
clinicians’ integrity with regards to deceiving patients.
5.6
A counter argument in considering the burden on practitioners is that
holding such information is part of their duty to the patient and that
respecting the wishes of their patient should be their uppermost
consideration. In addition, it may be argued that patients who consent
to PGD with non-disclosure are likely to consider being deceived a
preferable option to finding out their genetic status.
Risks of inadvertent disclosure
5.7
There are a number of risks of inadvertent disclosure of a patient’s
genetic status following PGD with non-disclosure. This would be
especially problematic in large centres where there were numerous
different professionals involved in caring for the patients. Consideration
would need to be given to how many members of staff would know the
test results, how patient care would continue and how the clinic could
ensure that information would not be passed onto the patient in subtle
ways, for example, through body language. Clinics would be required
to have sufficient safeguard measures to ensure that information is not
accidently disclosed to patients i.e. through medical notes and records.
Dummy embryo transfers or embryo tests
5.8
PGD with non-disclosure may also result in cases where all embryos
created and tested would be unsuitable for transfer to the uterus.
Although the embryo may be unsuitable for transfer for a number of
reasons, patients may assume that this result implies they have the
condition in question. Clinicians may fully explain to the patient that the
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problem was with the IVF cycle; however, some clinic may instead
perform ‘dummy’ embryo transfers.
5.9
Dummy embryo testing may also be required for subsequent rounds of
IVF where clinicians are aware that no risk exists to the embryo, but
this cannot be disclosed. Inadvertent disclosure could occur if patients
were informed that PGD could not be carried out because no
‘particular’ risk existed to the embryos (as set out in the Code of
Practice).
5.10
Both ‘dummy’ procedures present ethical issues with regards to a
patient’s ability to consent to deception, and the unnecessary tests,
risks and costs involved with the patient undergoing ‘dummy’
treatment.
5.11
The Committee may wish to consider whether such deception could
ever be justified and the risks this could have for the doctor-patientpartnership outlined by the GMC, in which relationships should be
based on ‘openness, trust and good communication’.
6. Professional Guidance
6.1
The European Society of Human Reproduction and Embryology
(ESHRE) Ethics Task Force published a report on this issue in 2003.
6.2
The taskforce recognised the right of the parent not to know whether or
not they are themselves affected while enabling them to have children
not affected by the disease. The taskforce concluded that the exclusion
testing had the same ethical consideration, in terms of the loss of
embryos, as PGD for sex-linked conditions. However, they advised that
genetic implications counselling would be a necessary part of the
procedure. 5
6.3
The taskforce considered that non-disclosure PGD imposed unethical
behaviour on the practitioners and negatively affected their autonomy.
The report concluded that it would be advisable to test only the
embryos of couples who agree to know the results and who accept all
the implications of the test.6
7. Possible methods for regulating
7.1
As referred to in section 3.2, the HFE Act 1990 (as amended) requires
the Authority to authorise testing for an abnormality, rather then
authorising the method of testing. In light of this, the Committee may
wish to discuss the possible methods for regulating PGD with nondisclosure if minded to do so.
5
ESHRE Ethics Taskforce 5: preimplantation genetic diagnosis – report F. Shenfield1 et al
ESHRE Ethics Taskforce 5: preimplantation genetic diagnosis – report F. Shenfield1 et al
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7.2
The advice from the internal legal department is that if the Authority
decided that the practice of PGD testing "with non-disclosure" was not
considered to be the proper conduct of a licensed activity, it could
either:
(a)
(b)
impose a licence condition prohibiting the practice; or
issue strong guidance about the ethical considerations and leave
it to individual clinics to determine whether or not disclosure
should be made in particular cases.
8. Summary
8.1
Key Points - Exclusion Testing
Allows patients to have children free of the risk of inheriting a
condition, whilst protecting the patient’s ‘right not to know’
Medical professionals do not find out the genetic status of the
patient (or partner)
Loss of embryos is equivalent to PGD for sex linked conditions
which is widely accepted and enshrined in law
8.2
Key Points – PGD Non-Disclosure
Doctor’s duty of care and integrity may be questioned i.e.
performing unnecessary medical treatment and deceiving
patients
Burden of knowledge on professionals who become aware of
the patient’s genetic status
Risks of inadvertent disclosure/problem of fire-walling
information from the patient and other medical professionals
9. Recommendations to the Committee
9.1
Members are asked:
To discuss the licensing of exclusion testing, and to recommend to the
Authority that this method of testing is acceptable.
To discuss the additional ethical issues pertaining to PGD with nondisclosure as a method of testing and recommend either:
(a)
a licence condition prohibiting the practice; or
(b)
strong guidance about the ethical considerations, leaving it to
individual clinics to determine whether or not disclosure should be
made in particular cases.
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