Examination of Witnesses (Questions 1060
- 1079)
WEDNESDAY 24 NOVEMBER 2004
PROFESSOR ROBERT
EDWARDS, PROFESSOR
CATHERINE PECKHAM
AND PROFESSOR
HENRY LEESE
Q1060 Dr Iddon: It sounds, Professor
Peckham, as if you are saying that we need a regulatory body but
there is something wrong with the HFEA so can I tease out of you
how you perhaps would improve the regulatory body, if it were
an expansion or a development of the HFEA or a completely new
organisation, and I would ask the other witnesses to throw their
ideas in too.
Professor Peckham: I am probably
not the one to say how that should be done but I think that the
science underpinning might mean that you need more careful regulation
of the early assessment of some of the new technologies so that
you might license for limited use for a duration of time while
information is accrued, and that you get the proper evaluation
before it is more widely used across clinics. I think probably
Professor Leese would be in a better position to answer that.
Professor Leese: I would agree.
We were able to give either a red, amber or green light to the
new advances but we were not really then able to follow them through
as they were being practised in the clinics, and clinics do things
in different ways. If we had a more systematic approach to following
through the recommendations that HFEA made you could do a lot
of research, but you would need input of probably a different
mix of researchers who were experienced in doing randomised studies
and trials, etc, so we would recommend something and attempt to
see it was followed through in the clinic but we were not a research
body, and could not dictate the research they should do, but there
is a lot of different practice going on out there and if it was
managed more effectively we could get a lot of data on how these
different procedures work.
Q1061 Dr Iddon: Do you think the
HFEA are trying to regulate things that should have been passed
on to other bodies like the other regulatory medical organisations,
for example, IVF? We have had the view presented to us that IVF
is such routine medical practice that really the HFEA should hand
it on to the other regulatory organisations and concentrate on
the newer technologies.
Professor Leese: I do not feel
very strongly about this. As long as the system is in place I
am not a what-is-the-best-way-to-regulate type of person. I am
a great believer in getting the best people that you can get round
the table and coming to a decision. As to how that is, as it were,
systemised or put into practice I do not have a strong view on.
The HFEA when I was on it did its best with limited information,
and that I thought worked quite well. I do not feel strongly whether
this part of its function should be given to someone else.
Professor Edwards: Could I make
a comment? I think the introduction of ICSI is an example of what
you may be searching for. That was discovered by accident and
within three months it was crossing the world, not only Britain.
I was amazed that it worked—I still am but it does work.
There was never any foresight in what might happen to that. The
second example which may be more relevant is that some of our
American friends—
Q1062 Dr Iddon: Could I just interrupt
you and ask do you think the HFEA held back the development of
ICSI?
Professor Edwards: I think it
probably came in just before the ICSI was formed.
Professor Leese: No, it was not.
1993.
Professor Edwards: ICSI was 1991,
I think.
Professor Leese: I felt they could
not have done. It worked. Infertile men were being able to have
babies and the floodgates were opened. It would have been inconceivable
to stop it. In an ideal world you would; you would have gone back
to animal studies, work on surplus human embryos, work on clinical
trials. Ten years later, the green light. It is now 50% of all
practice in the clinics. It would have been impossible on emotional,
pragmatic, and practical grounds to stop it.
Q1063 Chairman: Legal grounds as
well?
Professor Leese: Maybe.
Professor Edwards: The group that
has done more to follow up ICSI is the Belgian group, headed by
Andre van Steirtighem and Paul Devroey, that started it and I
would say if you wanted an example of a clinic that is incredibly
responsible, that is Professors van Steirtighem and Paul Devroey
in Brussels, where their follow-up studies have been astonishing,
and I take my hat off to them. But also to your point, a technique
came in five days ago of seeing if you could donate ovaplasm from
a good egg to a poor egg. It ran into a problem with mitochondria.
In relation to the question you asked, the FDA in the States called
it in. Now, they have the power to call researchers in. I know
that many of my colleagues were very apprehensive about what might
happen in the committee. In the end the FDA did a thorough study;
decided there was no adverse evidence; and said, "Carry on
with caution or report back". I think that is what you are
getting at actually, and the model I would strongly suggest you
go to is the American FDA, the Federal Drug Agency, which is responsible
for all drugs but now responsible for all new techniques, and
not only drugs, so I think it is the organisation you are looking
at.
Q1064 Dr Iddon: What I am really
getting at is a simply yes or no. Do any of our witnesses feel
that the HFEA have held back, first of all, research and then,
secondly, the translation of that research into a medical practice?
Professor Edwards: No.
Professor Leese: It has always
been one of the pillars on which it has worked, the HFEA, the
need to promote good research, to get a good evidence base as
with any area of medicine, along with welfare of the child, respect
for the embryo, for example. The need to promote research has
always been there and as someone who has had a research licence,
even a voluntary licence prior to the Act, I have had firm management
of the licence and rigorous application but I have always been
encouraged to do research.
Professor Edwards: Could I amplify
that comment? In two years before the HFEA developed as a scientist
I had to bring a libel action in the High Court in London against
the BMA, BBC and several newspapers. We were right in the forefront
of ethics. If you argued you went to law, there was nothing else.
If you made a decision and somebody did not like it, they were
able to sue you. The HFEA ended all that and I would say since
then that we in Britain have been very lucky indeed, and I really
want to state that, because when I go abroad the admiration of
the HFEA is unbounded. Many countries have copied it, copied us,
yet if the HFEA makes a decision, in my field—I do not know
if it goes to the public at large—the decision goes around
the world. That is what we have created in Britain. I think we
should be very proud of it but I do agree with you that you may
need an FDA as well that takes over the research once it is under
way. I think I would agree with you on that one. But the HFEA
to me has been fantastic. We have disagreed with them. We disagreed
on the second case of the designer baby. There was a child's life
at stake—to me that is number one, and it did not seem to
be number one with the HFEA, but there may be a reason for it,
and I know they gave reasons at the time. So that is where we
stand. The HFEA I think has been wonderful.
Q1065 Dr Harris: What was the reason
they gave at the time?
Professor Edwards: I have to think
back. The case was not a definite genetic case. It may have had
environmental effects.
Q1066 Dr Harris: Were you on the
HFEA at the time?
Professor Leese: I was on then.
They were concerned about the risks of biopsy and the super-ovulation
on the woman, and that until there was long term or better evidence
for the safety of the biopsy technique that would be required
they should delay on this one. I think eventually they got it
right, but it was a kind of precaution when it first came to the
authority, if I recall.
Q1067 Dr Harris: Yes. Now, I would
like to ask the panel, on that issue, because we have just been
talking about the use of evidence by the HFEA, in the Whittaker
case, as you say, they say that they said that they were not going
to allow the existing child to be treated in this way because
of the risks of biopsy, and then they changed their minds on a
later case. Was that because, in your view, the science had changed?
That there was a study published in the interim that showed that
the biopsy was safe?
Professor Leese: I think I came
off the authority at that point—which is not a very good
excuse. I think there was a general rethink and maybe the climate
changed as well. You would really have to ask the people who made
the subsequent decision. I think the prevailing culture had been
"If we are not very happy, we will say no". I really
believe that. We are desperate to help these couples but if we
feel there is a problem it is beholden on us to say no, and I
think the first time round there was a lot of novelty to it.
Q1068 Dr Harris: But the Whittaker
child could have died, so some people argued you have to have
a good reason to adopt a cautionary approach even though PGD had
been going on for a while and there had been no—
Professor Edwards: The risk of
damage to an embryo by taking a cell off appears to be minor,
if at all. The embryo is able to adjust. Secondly, the case that
they made against going ahead was that they wanted clear-cut cases
where there was a clear gene involved and not something else that
may or may not happen. I cannot remember the situation that may
or may not happen in this case but you will find it in the HFEA
report.
Q1069 Dr Harris: But they had a similar
case where there was not a gene involved that they could select
out?
Professor Edwards: Yes. Now, when
that same couple who had been declined because it was purely genetic
went to the States, the case was done immediately by a group over
there. So this ended happily but at the time I thought the HFEA
made a mistake. If there is any risk to a child I think you go
ahead. That is my own feeling.
Q1070 Dr Harris: So to generalise,
what is your view of the way the HFEA uses clinical evidence in
supporting policy decisions? That is one example. Ending donor
anonymity is another; the number of embryos transferred.
Professor Edwards: Yes. If it
was strictly clinical evidence in this question I would say they
have very good advices. The scientists on the HFEA are no pushovers.
They will judge on the evidence. It is usually the social side
I think I disagree more on. In the case of Diane Blood, in the
case of this DBA baby—but these are very rare cases. On
the whole the HFEA handles the clinical evidence properly and
the scientific evidence properly.
Q1071 Dr Harris: Professor Peckham,
do you agree?
Professor Peckham: I think they
have very good expert advice when making individual decisions
and they are very science-aware but I think the climate changes
and I think, as already mentioned, there are social factors that
come into this, not just science.
Q1072 Dr Harris: It has been well
known, for example, that multiple embryo transfer gives a significant
risk obviously of multiple births and that the outcomes there
are poor, and other countries in Europe—Sweden, for example,
is very clear about single embryo transfer, has higher success
rates than we do per cycle I understand, although I know it is
hard to compare like with like but in the ICSI data we have seen,
so why did it take so long for there to be even the limits there
have been in this country on multiple embryo transfer?
Professor Edwards: Louise Brown
was a single embryo transfer. When we started we did single embryo
transfers for years because we thought the human embryo was the
same as animal embryos. It turned out that only 15% of all human
eggs will implant. We are in a disaster area here so you have
to select the embryos, and we now know how to select them—just
to find the 15%. So the single embryo transfer has been on the
cards for a very long time. The Scandinavians advertised it but
other people did it as well, I would say.
Professor Leese: I think with
hindsight the HFEA could probably have moved a bit quicker to
lower the limit from three to two and I suspect there is no question
eventually we will go to single embryo transfer. It is a matter
of when that happens. I think they could perhaps have gone a bit
quicker. There were some quite vociferous complaints from some
clinics that this was going to reduce success rates, which of
course it would do, but I think they could have moved a little
bit quicker. But they are there now and I think they will go to
single embryo transfers eventually.
Professor Edwards: May I say I
would not accept a criticism of the HFEA on this score because
it came in slowly, as various nations moved towards it. Finland
deserves a lot of credit here but it was on all our agenda. We
wanted go to two and one embryo transfers, if we could. It became
possible when we knew how to select the best embryos. Then it
became possible. Now, that was the breakthrough, and that breakthrough
started about 1990 or something like that. That is when it became
clear you could transfer single embryos and get 50% pregnancy
rates and that was the breakthrough. Without that you were forced
to transfer two or three. There was no other way round it.
Q1073 Dr Harris: Lastly in this area
is my question about whether the HFEA or societies should restrict
clinics from offering treatment and tests where the value and
outcomes are still unclear. One example might be anuploidy screening
where there is not a huge amount of evidence to suggest that it
increases the chances of a live birth, but it is being offered
by some clinics. Should we say "Wait, stop, let us trial
it in some areas", or should we say "Let's just give
information and allow patient to make the choice with their doctors"?
Professor Edwards: I think you
met Dr Verlinsky in the meeting. He has done now 5000 cases I
think—well, maybe not that number but an immense numbers
of chromosome analyses on embryos, and the group led by Jack Cohen
and Santiago Munne must have done about the same. These are two
American groups. We have done very few in comparison. Their data
I think, and I have to agree it is recent, is getting very convincing
indeed—that you reduce the number of abortions because you
select out those who are going to abort. You choose the best embryos,
so even some women of 42 have managed to have their pregnancies
where before they may never have had them, because they only have
one embryo in ten to transfer. This is the situation we are in,
you see.
Professor Leese: It has to be
said, though, that there was a large study in Belgium which was
the first really properly randomised study that showed no advantage
so I think the jury is out on aneuploidy screening, and I think
it rather picks up your question. It is very difficult to know
what to do. HFEA license it in a few cases. I think it would lend
itself to the sort of approach that Professor Peckham's committee
are advocating where you follow the procedure much more rigorously
once it has been started. I think HFEA would allow it and we would
have reports back but in no way was this a systematic examination
of this new technique, and I think that is where your work would
come in really well.
Q1074 Chairman: Very quickly, on
the licensing process itself is there too much peer review in
the licensing process, including the funders, and is the Freedom
of Information Act going to make a difference too about information
and the anonymity of reviewers and so on, and should the funders
be encouraged to apply criteria set out by the HFEA before funding
research projects? There are changes going on in licensing applications.
Professor Leese: What was the
last one again?
Q1075 Chairman: When you fund something,
should the criteria set out by the HFEA be picked up by the research
funders as well, or should they just ignore them?
Professor Leese: I think there
needs to be a dialogue between bodies like the MRC and the HFEA
because much of what we said obviously costs money to get the
evidence base where if it were in better shape it would cost money.
I think there is no question about that. But it still comes back
to the HFEA not being a research body. That is not what it was
set up for.
Q1076 Chairman: You can see what
I am driving at. There is too much of it going on. Why do they
not get together and form one body?
Professor Leese: The HFEA requested
that your committee be formed.
Professor Peckham: I think that
showed great responsibility and I have heard nothing but good
about the HFEA, particularly internationally. I think it showed
responsibility to come to the MRC because of their concern that
they wanted to ensure that the scientific evidence—
Q1077 Chairman: Let me cut the cackle.
Should the HFEA have a research function, do you think? You have
investigated it. All the playing around, peer review to the right,
to the left, for the licensing application—why do we not
just give them the function and get on with it? If you trust them
so much, if they are so damned good?
Professor Leese: The HFEA were
so good because they created a climate in which this could operate.
I do not think they should be a research body.
Q1078 Chairman: Why?
Professor Peckham: You cannot
do research in that sort of environment. You have to have the
scientists working together; you have to have the back-up for
research; you have to have the interdisciplinary groups—it
has a totally different function. Legislation is quite different
from a research activity.
Q1079 Chairman: You can have sub-committees
and sub-organisations?
Professor Leese: I can see them
putting up the projects for tender maybe and then you would have
to have the MRC or even the department responding to the tenders
and saying "This is the project I would seek to—
Chairman: I do not think we have thought
this out at all. There are too many people with fingers in the
pie, I think. You may disagree but that is how I am reading things.
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