Examination of Witnesses (Questions 280
- 299)
TUESDAY 14 DECEMBER 2004
PROFESSOR PETER
FENTEM, PROFESSOR
PETER WEISSBERG
AND PROFESSOR
KENNEDY LEES
Q280 Lord May of Oxford:
So, from the point of view of the NHS budget, comparing the cost
of looking after people who could have been in much better shape
if they had had better care, you are suggesting that, even in
purely brutal cost-effective terms, it is better to spend more
money on this?
Professor Lees: Let
us look at the numbers. The use of statins to prevent stroke may
cost about £20,000 to prevent one stroke; to treat a stroke
when it has occurred—one, average stroke patient's time
spent in hospital, looking at the hospital cost—is maybe
£10,000 to £15,000. To give acute treatment with something
like thrombolysis, at £400 for one patient's treatment (you
need to treat around eight to get the benefits), it is £3,000
or £4,000. So you are saving money by getting in there early
and doing as much as you can. I am not saying that is all you
need to do—
Q281 Lord May of Oxford:
That is not the only consideration, but it is interesting way
of looking at it.
Professor Lees: And
it certainly will not work for everybody, but this is a very important,
very cost-effective argument.
Q282 Chairman:
While you have the floor, do you want to continue on the priorities
in scientific channels?
Professor Lees: I
think the priority is to apply what we have already learned. We
have learnt a lot about prevention, and we still have people out
there in the pubs and clubs smoking—and perhaps that will
change shortly—but there is a very powerful thing that we
could do to help reduce or delay stroke and heart disease. It
will help other conditions as well. We have learnt about acute
treatment, we have learnt that stroke unit care does make a difference
but we have not yet worked out how to get everybody into these
units; we have learnt that we can examine stroke and tell: "Is
it ischaemic or haemorrhagic?" In fact, there are indications
that both can be treated by different mechanisms early, but we
are not yet applying that. We have learnt that by using imaging
we can discover much more about the mechanisms that are going
on and, therefore, we can discover whether some of the mechanisms
that seem to work in animal experimentation could be useful for
stroke—whether these do apply and, therefore, we could target
our research and our treatments better in that. However, we have
huge barriers to research, and stroke particularly. Barriers include
the fact that stroke is a heterogeneous disease and that by the
time somebody has a stroke they are already reasonably old and
they may well have other conditions. These other conditions and
the variation in care they get make an enormous difference to
the outcome, so we need very large trials; trials of thousands
of patients to give us an answer. There are barriers to running
multi-centre trials, particularly in the UK. A research assessment
exercise measures us as academic clinicians on our individual
contribution to authorship of papers, our contribution to the
grants that we get, and only one or two people can get credits
for that but we need hundreds of people all round the country
contributing work to these trials. They get no credits for that
so they are disadvantaged as soon as they take part. Hospital
managers are not encouraged; there is no incentive for them to
put patients into trials because it tends to be more expensive
to put patients into trials; they have to spend a bit more time
with the patient and a bit more on imaging costs, so there is
disadvantage there. We need to start giving ourselves incentives
to take part in this sort of research.
Q283 Baroness Walmsley:
You talked about the multi-centre trials. Do the people in all
the different centres have to deal with their local ethics committee?
So have we got multiple ethics committees as well, or is it done
in one place?
Professor Lees: Let
me declare a conflict of interest here. I chair the Multi-Centre
Ethics Committee for Scotland—the one that deals with Adults
With Incapacity. There is no question that we have simplified
the ethics procedure, to some extent, but we have done it at the
cost of increasing the amount of bureaucracy in many other ways:
the forms that have to be filled in now run to some 60 pages.
This is partly due to the Central Office for Resrach Ethics Committees,
the organisation that has taken over the running of the ethics
system. We have a very cumbersome form-filling process and we
have to go through the R&D departments in individual hospitals,
whereas before perhaps they were not involved. We have all the
European Clinical Trials Directive mandates on the numbers of
forms that have to be filled, and if it is an academic study you
still need to have huge organisation there to be able to report
what we call serious adverse events—which, in most cases
for a stroke trial, are things that would happen anyway to the
patient—nothing to do with the treatment we are researching
but all to do with the complications that arise anyway. So we
have an enormous bureaucracy which is not all of our own doing
in the UK (some of it is thrust on us by Europe), but we have
applied it in a way that makes life very difficult. There are
very many people who would be interested in multi-centre research
who are now saying, "I just do not have the resources to
do this. It is too complicated".
Q284 Baroness Walmsley:
Is it done differently in England?
Professor Lees: England
and Scotland have exactly the same system; the only difference
on the incapacity issue in Scotland was that research not involving
drugs goes through a single designated committee rather than going
through any of the general committees.
Professor Weissberg:
It is difficult to know where to start. From the British Heart
Foundation perspective, I guess there are two major roles that
the BHF play traditionally. Let me just explain that the division
of our spend is approximately £50-£55 million on research
and about £15-£20 million on care and education. So
the remit is to fund the very best of the fundamental research
and clinical trials that are requested and required but, also,
to plug the gaps in clinical care. As an example of that (and
I mentioned heart failure earlier on) the Heart Foundation has
funded, through the New Opportunities Fund, 155 nurses to look
after patients with heart failure, because in effect hospitals
do not have the resources to do it. If you have a nurse who can
visit a patient at home and change the diuretic dose you can keep
that patient out of hospital, whereas if you do not that patient
ends up getting into end-stage heart failure and coming in as
an emergency with all the risks that go with it. The organisation's
spin on this is that we are interested in the fundamental
research underpinning cardiovascular disease but, also, the clinical
care that is required. I would echo the points made here by my
colleagues that there are two aspects to improving health care.
One is applying the very best of available medicines and evidence-based
medicines and evidence-based procedures, and I am afraid the UK
is extremely poor at doing so. We have known for about 15 years
now that thrombolycis, these clot-busting drugs, save lives in
heart attacks and the quicker you give it the more effective it
is. Only now, though, have we got to a position where patients
are getting it within about 30 minutes of the onset of their symptoms.
It takes a long time in our system for new evidence to be adopted
and to be translated. I think in terms of trying to prevent morbidity
in the elderly, one aspect—as has been said already—is
applying best practice quickly and efficiently within our health
system, and we have not been very good at doing that.
Q285 Chairman:
Can you say why?
Professor Weissberg:
Generally, cost, because all of the things you have heard about
involve up-front costs. Again, we have all put forward economic
arguments and mentioned "Is there a saving, ultimately, to
be made?" The answer is yes, there is, but not to today's
budget in that hospital. That is the way, I am afraid, the NHS
looks at it; they are looking at this year's budget in this hospital:
"If I keep a heart failure patient out of that bed somebody
else's patient is going to fill it". So the bed is still
filled, the work is still there, but in terms of future cost to
the NHS there is a large saving, but we do not seem to have the
flexibility to build that into the system. I think there has also
been, if you like, an inherent caution, which has not necessarily
always been bad in UK medicine, in that we do wait for the evidence
to be pretty overwhelming before we apply it, and I think that
is a benefit to the publicly-funded system; you cannot splash
money around on new techniques and new drugs if you do not know
that they work, but we need the clinical trials to show that they
work and—more importantly—once the trial is over we
need to implement that best practice very, very quickly. To pick
up on one of the other things that was mentioned earlier on, which
is imaging, imaging is becoming increasingly sophisticated. Time
was, not so very long ago, if you had a stroke nobody wanted to
image you, and speaking as a non-stroke specialist I think that
is probably right. Nowadays, if you go to the right places, as
has been suggested, and you get into the scanner very quickly
you will have an image taken of where your stroke is and what
is the vascular disease underlying it and, if you are luckier
still, somebody will intervene on that and open up that blood
vessel. However, there has been a leap of technology away from
catheter based, x-ray based imaging which means inserting a tube
into a vessel, infusing a dye and taking an x-ray picture—which
was invasive, moderately dangerous, costly and required a lot
of staff—to very slick, non-invasive techniques based on
Magnetic Resonance Imaging, position emission tomography and CT
scanning. As has been said, although most hospitals certainly
have CT scanners now and eye scanners what they do not have is
access, rapidly enough, for patients who need acute management;
they tend to be used for the chronic condition, and even then
you will wait, in some hospitals, six or nine months to have your
back MRI image or a joint MRI image because of the backlog. I
would echo what has been said about the implementation of what
we already know. That would go a huge way towards offsetting some
of the future problems that we have. As I said, from the point
of the BHF, we are very interested in the pipeline of what might
come along in the future and so we are particularly looking at
strategies that might either prevent or deal better with disease
that comes along. Another example which I have not mentioned are
the ventricular-assist devices. These are mechanical pumps that
can take over the work of the heart and have traditionally been
used to tide patients over for transplantation. In other words,
if a relatively young person with devastating heart failure has
been deemed worthy of a transplant but there is no donor, a mechanical
device is put in, which is basically a mechanical pump, which
does the work of the heart until such time as the transplant can
take place. These devices have been problematic because they cause
complications, but they have reached a level of sophistication
now where one can consider starting to put these devices into
people with a view to sustaining them long-term and taking over
the heart, and that is a technology which is advancing at quite
a rate. I think, if you like, with ventricular-assist devices
we are about where we were with pacemakers when I first started
putting pacemakers in: they were the size of your fist, with wires
about that size that you, somehow, had to manipulate under the
skin into the heart, and now they are the size of half a matchbox
with a very fine fibre which can be inserted in a matter of half-an-hour
and the patient can go home the same day. I think the assist devices
are liable to move in the same direction.
Q286 Baroness Walmsley:
I would like to ask to what extent your priorities are recognised
by government. Do you think there is a good link between science
and policy development? Do you think things could be done any
better and, if so, what would be the benefits?
Professor Weissberg:
I will talk about cardiovascular rather than cerebrovascular and
stroke, in that it has been a government target through the National
Service Framework, and that is one of the reasons that the times,
as I have already mentioned, in getting heart attack patients
treated have come down because it has become a government priority,
they have put money behind it and so things have started to happen.
If you like, it shows what can be done when the right impetus
is put behind it. There are coalitions of funders for research:
one, in particular, is the Cardiovascular Research Funders Forum,
which is a coalition of the Department of Health, the BHF, the
Wellcome Trust, the MRC, and the Stroke Association (I think that
is probably it) who meet relatively regularly to discuss strategy
and areas of research that are of importance. I think we have
got a way to go yet to make sure that that then gets translated
into implementation and funding but at least the infrastructure
is there to do that. I think, from the cardiovascular point of
view, we have been fairly lucky over the years. I think stroke
has been, unfortunately, left somewhat behind. I do not know whether
my colleagues would agree with that.
Professor Fentem:
I think there are a number of points worth making as regards stroke.
Stroke research has benefited from the NHS research and development
programme, there is no doubt about that, and they enabled us to
pick up some quite important projects in relation to rehabilitation.
The other area which is rather important and which we have not
touched on this afternoon is the question of research capacity.
I came to see Lord Warner in December and Lord Warner said to
me: "If I gave you £10 million would you know where
to spend it?" The answer is that we would have a bit of difficulty
in spending it in some of the areas which are our priorities,
for the reason that stroke is quite a new discipline. As I said
at the outset, 20 years ago nothing much was happening for stroke
patients; stroke research is therefore relatively new, certainly
compared with the research into heart disease. The result is that
there is a capacity-building exercise that is needed in order
to have the researchers around who were capable of undertaking
this work. It is a great pleasure to be able to say that the NHS
have, at last, picked that up. The Stroke Association is one of
the strands of their support that they have given. We have had
bursaries to help build research capacity for some years, but
the NHS have now picked that up. Indeed, the level of support
that was provided for such people was, I think, particularly generous,
which is slightly surprising.
Q287 Chairman:
It is not often we hear it said!
Professor Fentem:
So far as the MRC are concerned, it is only 18 months since stroke
was listed in their strategy. There was a meeting 18 months ago
of their overall research strategy committee and at that committee
it was agreed that stroke would appear in the strategy. It is
not easy, either, to disentangle what portion of the brain sciences
programme is relevant to stroke. So there is a sort of fairly
artificial exercise which goes on, as reported in Hansard
as to exactly how much money is spent on stroke research. The
hard facts are, I think, that the Stroke Association spends about
£2 million, the MRC probably about £4 million and over
a period of time of perhaps 10 years, the NHS has spent £15
million. That is against the £100 million spent annually
on cancer and larger sums of money that Peter Weissberg is now
able to spend on heart disease. We are now a member of the Cardiovascular
Funders' Forum but in the paper that I submitted, my Lord Chairman,
I pointed out that I was a member of the Funders' Forum for Research
in Ageing and Older People. That, I have to say, has been particularly
disappointing. I hoped that that would be the research component
of, if you like, the National Service Framework for Older People,
but it did not prove to be that. Of course, the reason it did
not work or has not worked so far is that there was not enough
money on the table. We were a collection of very small charities:
Help the Aged have about £5 million a year they spend, we
have £2 million, and that is in contrast with the £100
million that the cancer charities brought to the table—maybe
it is nearer £200 million now, I cannot remember. So there
was no prospect that we would have some quick wins and make a
big impact on research into ageing. That is a big disappointment.
So I suppose, in summary, some good support may come from the
NHS, particularly now with the National Stroke Clinical Research
Network but not so good in relation, at least, to the Funders'
Forum.
Professor Lees: I
think it is right that we do not have all that many green shoots
that are there, able to spend money. I can certainly find places
to spend £10 million very easily. I think we are growing
on stony ground—this is the problem—and the three
things I would say we really need to do to translate that apparent
policy of supporting stroke research into action are, first, to
deal with the bureaucracy that we talked about—the red tape,
the paperwork—second, to deal with that issue of incentives
for multi-centre work (that is both remove the disincentive that
if you are doing that you do not get points in the RAE, and add
an incentive to the hospitals and the NHS system to encourage
research), and, third, let us deal with the infrastructure. That
involves two things. One will cost money, and that is putting
in more in the way of imaging equipment and more in the way of
radiologists and radiographers to run that equipment, but the
second part need not cost money, and that is to say it will be
government policy that every patient with stroke and every patient
with heart attack will, when they come into hospital, be immediately
diagnosed. So, for a heart attack patient, that may be that they
get their ECG—done, and I think we would think it would
be dreadful if you could not get a cardiograph done when you turned
up at hospital with chest pain- and for a stroke patient it means
an immediate scan. Right at the moment, the target is to get your
CT scan within a couple of days—two days, for a condition
where the brain is dying over hours.
Q288 Baroness Walmsley:
If I may, my Lord Chairman, I have a little follow-up. All three
of you gentlemen have talked in your response to my question about
priorities about the structures and systems in place to set the
priorities for research, with the exception, perhaps, of Professor
Lees. I wonder if you can say something about the structures and
systems that are in place to identify the priorities about implementation
and best practice, and all those things. In your earlier answers
you were lamenting the fact that a lot of the research does then
not translate into better practice and systems to actually deliver
the results of the research to the patient. Who decides now?
Professor Weissberg:
In theory and in practice it is probably the National Institute
of Clinical Excellence these days that decides. So once a new
development is recognised out in the medical literature then it
goes onto the agenda for NICE to adjudicate as to whether this
is value for money within the NHS, and until that point is reached
it is nigh-on impossible to introduce a new medical technique
or system, even though the evidence is out there, because the
funding is not there. The theory is, of course, if NICE approve
it then the funding should be made available, but at a practical
level we find in hospitals the money has to come out of a pot
which is held in the Primary Care Trusts, and most of them are
in the red. Even though we hear that NICE has said that such-and-such
technology should be instituted across the board it has to be
done at the financial disbenefit of that hospital. I will make
one other point, though, which is going back to research in implementation:
there is no doubt, in my mind, that the very best way to ensure
best practice is adopted is to be doing research in that area.
If you are doing research into stroke and acute thrombolycis you
have to come up with a strategy to get your patients into that
hospital to do that research within the minutes that you need.
Once you have set that up and you have shown that it works, then
generally speaking there is a moral imperative locally to make
sure that you follow on. So one should not under-estimate the
importance of clinical research in actually progressing clinical
practice. It is no accident that the centres of clinical excellence
are also the centres of research excellence because those are
places that gather the patients up, that put them into research
protocols, that brings them outside the rather turgid mechanism
of the health service and into a research protocol which allows
you to treat them quickly and get an answer. Even if you then
have to wait for NICE to agree, it is pretty unusual for you,
the local hospital that has discovered that treatment, not to
carry on using it.
Q289 Baroness Murphy:
Two things, if I may, following up that. One is, as Professor
Weissberg pointed out, the National Service Framework on Cardiovascular
Medicine has been very successful in concentrating the health
service's mind on the right targets in that area. I wonder why,
and perhaps Professor Lees and Professor Fentem might like to
comment, the National Service Framework for Older People did not
include best practice in relation to stroke. Yes, it has acute
stroke units and good things in it but no targets were set and
certainly not a very ambitious target.
Professor Lees: I
am not sure I can answer that question, but if I can throw a question
back to you: why was there not a National Service Framework on
strokes specifically, given that it is the third leading cause
of mortality and is a major medical cause of disability, etc,
etc? I think stroke was put in as an after-thought to that. In
England, just as in Scotland, we had stroke added to the cardiovascular
disease document in much the same way; it is seen as the poor
brother or sister.
Q290 Baroness Murphy:
It is all wrapped up in things "elderly".
Professor Lees: Just
tagged on at the end, yes.
Professor Fentem:
I think we should say that Standard Five of the NSF for Older
People has had its effect. I had made some notes on what I thought
the links were. I have, for my sins, also served as a non-executive
director of a PCT, and in the discussion there Standard Five of
the NSF has certainly had its impact. One of the most important
links has been the publication of the Royal College of Physicians'
Guidelines on Stroke, which are evidence based and which have
identified those areas in stroke across the clinical spectrum,
from acute care to community care, where we have evidence and
where we do not. It seems to me that that is a particularly valuable
contribution (the recent edition 2004 has just been published),
and that has had a tremendous impact on stroke care, and will
continue to do so. May I just say, in support of Professor Weissberg,
I welcomed John Reid's pronouncement that good research equates
with good care, and good research saves lives. It has been demonstrated
for cancer and we hope now that we might have the opportunity
to demonstrate it for other conditions including stroke.
Q291 Lord May of Oxford:
I want to pick up on something you have just said about the connection
between basic, clinical research and the delivery of universally
effective care based on that. I do realise that simply counting
papers and things is not a reliable measure of the quality of
work, and I do realise that there are differences in the quality
of work in the different hospitals. Nonetheless, clinical research
measured both by quality of papers and measured by relative expenditure
on it by conventional methods, is something in which the UK is,
for example, well ahead of Canada, which was the one that manages
to put things better. Thirteen per cent of the world's clinical
medical literature is produced by the UK. I realise there has
been a certain amount of decline in this, and I repeat myself
that I realise it is not the only measure, but I offer it back
to you as something that casts a bit of a shadow over the statement
that if you are really very, very good at doing research that
means you will be very good at looking after the patients, because
it seems to me that our failure is not a failure in the research
as such but a failure in the effective delivery of it.
Professor Weissberg:
Perhaps I can respond to that. I was not suggesting it was a failure
of research, I was suggesting that if you are prosecuting good
clinical research then that necessarily has an impact—
Q292 Lord May of Oxford:
At the place where you are doing it. Therefore, I draw the conclusion,
everyone has to be doing the basic research otherwise hospitals
will not be doing a good job.
Professor Weissberg:
I am not implying that. I said the centres of excellence that
produce the research are doing the best clinical practice, by
and large—not totally—and so what I was saying is
that those centres that wish and are able to do the research need
to be able to do it, and as we have heard there are big barriers
to doing that. Going back to Lady Murphy's point about the impact
of research, the NSF for Cardiovascular Disease was a somewhat
easier nut to crack than, perhaps, many others because we had
good evidence. So we could say we know that it saves lives to
give aspirin, therefore that has to be one of the goals for the
NSF. We know that streptokinase save lives, we know that ace inhibitors
save lives and we know that statins save lives, and I would make
the point that we know that because of studies done in the UK
in our major centres (funded, I have to say, largely by the British
Heart Foundation) that have added that dot to the I or cross to
the T that says "Yes, this piece of evidence is incontrovertible,
we must use it as best practice". It therefore went into
the NSF and now the standard of care is vastly better for patients
with cardiac disease than it was five to 10 years ago, but it
is because we have that body of evidence which came out of the
research that allowed us then to apply it. I think part of the
problem with stroke has been—and, again, I am saying this
not as a stroke specialist but, if you like, as a medical generalist—that
even 10 years ago the GP would send the heart attack patient immediately
to hospital because he felt they could do something for them,
and the stroke patient would stay at home. The hospital was not
seeing the immediate morbidity and problems associated with stroke
in the way that we were as cardiologists in our coronary care
units, and there is nothing like seeing a patient deteriorating
in front of your eyes to stimulate you to want to do something
about it. I think the problem with stroke has been that stroke
patients have largely been left in the community and it is only
now that we are starting to realise they are better cared for
in hospital. As the pendulum swings towards bringing more and
more stroke patients into hospital and sooner then I think the
impetus and the whole research agenda will accelerate, and I think
that is what feeds into the whole process.
Chairman: We have
quite a number of questions we would like to pursue so I am quite
keen to move on.
Q293 Lord Turnberg:
Professor Weissberg, you very helpfully pointed out that the brain
and the heart are pretty strong organs and if their blood supply
was okay they would do all right, that you should not be worrying
about them ageing and that the major problem, at the moment certainly
and for a long time to come, is ensuring that the blood supply
is okay and preventing atherosclerosis. This is all about preventing
disease as against studying the basic biology of ageing. This
may be a somewhat philosophical type of question but do you see
somewhere in here the problem of doing basic research on ageing
brains and ageing hearts irrespective of this disease-related
deterioration due to vascular disease? Is this a silly thing to
be thinking about now?
Professor Weissberg:
No, it is not but it is quite a difficult thing to do in that
it is difficult to get your hands on the organs that you want
to study in that particular age group. That is why I mention imaging
as being so important, because I think that with more investment
in research the non-invasive imaging techniques are beginning
to give us a handle on molecular mechanisms and cellular mechanisms
in the brain and in the heart, and I think that will then unlock
the ability to ask about the ageing process per se in the
brain cells and in the myocardium. There certainly already is
research going on into the association between atherosclerosis
and vascular ageing. One of the prevalent theories at the moment
is that a consequence of atherosclerosis, that is the plaque breaking
down to cause a stroke or a heart attack, is the failure of the
repair mechanism in the vascular wall; that there is a constant
tension between the lipid causing inflammation leading to the
plaque rupturing and the smooth muscle cells working as repairers
keeping that plaque intact and stopping it breaking down, and
there is clear evidence that the cells from a plaque, the smooth
muscle cells, are senescent. By that I mean if you try to make
them grow and divide they do not do so, they have reached the
end of their natural lifespan. There is molecular evidence now
to show that as cells divide (it does not matter which cell you
are talking about) the chromosomes get shorter and shorter and
shorter with each division until there comes a point where the
cell will no longer divide again, and some cancers occur because
that shortening never takes place. There is now evidence coming
out in cell biological literature that there may be, if you like,
premature senescence at a cellular level. It is not quite the
same thing as you are driving at in terms of ageing, but it is
trying to get at the fundamental biology of ageing, if that is
what you mean. I think there is quite a lot of mileage in that.
The other example I would cite is something from my own research
group's work, and that is Progeria Syndrome. These are these very
unfortunate children that age extraordinarily rapidly and die,
usually, at the age of 10 or thereabouts looking as if they are
80 or 90, but they die actually of vascular disease; it is that
which causes them to die. It is not in the context of conventional
risk factors for atherosclerosis—they do not have high lipids
or anything like that—but they do have rampant atherosclerosis
which kills them. The genetic cause of Progeria has just been
identified as lamin mutations, and that has opened up a whole
area of research. Lamin is a protein in the nuclear envelope which
binds to a whole host of other proteins, and so that has opened
up a whole area of cell biology and molecular biological research
asking how do these proteins interact to prevent cells from becoming
senescent under normal circumstances? Clearly, if you disrupt
one of those proteins that cell becomes senescent very rapidly.
So I think there are several indirect ways, if you like, into
the biology of senescence or ageing, and I think that is already
going on to an extent. Clearly, it is an important avenue of research
if one wants to understand the natural process of ageing.
Q294 Lord Turnberg:
Just as a follow-up on that, Professor Lees said we are going
to die of one of either cancer, heart attack or stroke. I am not
sure he is right because it is quite possible that in a number
of years' time most of the common cancers will have been cured
or prevented, and if we work on the vascular tree in the ageing
process in the way you have described and the arteries remain
patent and open and our hearts beat away nicely and our brains
continue to function, it may be something else that kills us off.
This is where the biology of ageing is going to be of importance.
Professor Lees: Or
the lack of pension!
Q295 Baroness Murphy:
The specific research you are talking about, looking at the cellular
and molecular level in relation to the ageing phenomenon, has
that been yet applied to the vascular system specifically? Do
we know whether, as yet, that work has been done or is it still
in the pipeline?
Professor Weissberg:
It is being applied to the vascular system. There are groups around
the country—my own group in Cambridge has certainly been
doing some work on this and I know of about four or five other
groups that are funded through the Heart Foundation—that
do research on the phenomenon of vascular ageing as opposed to
vascular disease progression.
Q296 Baroness Murphy:
Are those two regarded as separate?
Professor Weissberg:
Atherosclerosis is a disease associated with the ageing process
but it is not unique to ageing, so it is not inevitable that as
you get older you will get atherosclerosis nor is it inevitable
that if you are young you will not get atherosclerosis. I think
there is a distinction between the disease entity and vascular
ageing. If one took atherosclerosis away—and of course it
is very hard to do that in our society because pretty much everybody
has got some of it—then you are talking about the haemodynamics
of the stiff artery because there is no doubt that arteries get
stiffer as they get older, and if the main conduit artery, the
aorta, is stiff then it transmits much higher pressures to the
tissues beyond and they can damage the tissues beyond—the
brain, the kidney and the small vasculature—and I think
we have been less good at getting a handle on that process. That
is beginning to happen, again, partly through the new approaches
to imaging and, also, I have to say, because it is no longer unfashionable
to say "I am interested in physiology". There was a
time, 10 years ago, when you had to be interested in molecules
or cells to get any research funding at all, and if you said "I
want to do more research on the haemadynamics of how a blood vessel
behaves" you did not get funded. Fortunately, that pendulum
is beginning to swing back now and we are starting to understand
a bit more of the physiology—and we have got to because
we are learning a lot about molecules and a lot about the cells
but we have got to marry that with the physiology to be able to
understand how it all works out. I think there is more work going
on in that area.
Q297 Lord Soulsby of Swaffham Prior:
We have heard from you gentlemen about heart disease and stroke
and they are, clearly, seen to be priorities in the National Health
Service and in the pharmaceutical industries. Is there sufficient
co-ordination between clinical medicine and pharmaceutical companies
in either the treatment of the conditions or the prevention, and
if not how does one bring them together more effectively?
Professor Lees: I
have worked with industry—not in industry but I have worked
closely with them—and I think it is clear that industry
has contributed enormously to the health service, and vice versa
in terms of prevention. So that many of the drugs that have been
developed, the statins and the anti-hypertensives and so on—vast
numbers of drugs that have been looked at for preventative purposes
in thrombin—were developed by industry, and industry benefited
by getting the sales of these drugs, to the extent of enormous
sums of money. But, I think actually there is still a huge barrier.
As far as I can see there is no position where industry comes
to the health service and says, "We want to work together
to develop something". There is almost the opposite reaction;
that if industry wants to work with clinicians to do a trial the
health service puts barriers in the way by, for example, increasing
the costs. If the Medical Research Council wants to run a trial
in a particular hospital then the costs that are applied are those
of doing the research itself, the added cost, plus, maybe, a little
bit of overhead. If industry comes along, then every test that
would have been done anyway in these patients is charged at as
much as possible to the industrial company. So it is seen as a
way of extracting money from industry to support the health service.
Certainly there is nothing in the way of our research assessment
exercise or the incentives for anybody to take part in industry-funded
research; it is seen as being a bad thing to be doing. Yet, clearly,
it is necessary; we have to work in partnership with industry.
They very often have access to the compounds at a very early stage
of development, they have access to groups elsewhere in the world
who are willing to work with you; they can co-ordinate things,
they have the facilities for dealing with the bureaucracy of getting
compounds into different countries, and so on. So I think it is
necessary that we work with them but I do not think we are doing
it as well as we should do.
Q298 Lord Mitchell:
It is quite startling to hear that and I just wonder how would
you improve it if you could.
Professor Lees: The
research networks that are being set up will help with that because
they have been set up with an aim that they will encourage industry
research. I think we also have to put something in the way of
incentives in place for hospital managers to say "We want
you to take part in this"; we have to put it in place with
academics to say, "You will be given brownie points in the
RAE, or whatever, which will be worth as much as taking part only
in Medical Research Council-funded research". I think it
is to do with sorting out incentives. Then, I think, we have got
to go to industry and say, "Look, if we collaborate closely
with you, if we give you the lower rate for conducting research
in this country, we expect also to get the drugs sold to us at
a lower rate". I think we can work in partnership happily.
Professor Fentem:
I think the question is whether the present arrangements, in fact,
are optimal. As Lord May will detect, we have been looking carefully
in recent times at the Canadian stroke network. I think there
are some features of the network that commend themselves. Whether
it is too late to consider them for this country or not,
I am not sure. The pharmaceutical companies actually contribute
to the network, so the funding they put in the direction of research
goes to the network and is not, therefore, distributed on the
basis of contracts with individual clinical academic units, or
whatever. That, it seems to me, has something to commend it and
we need to move in that direction if we are going to make a real
success of the clinical research networks.
Q299 Lord Soulsby of Swaffham Prior:
I was going to come to the clinical networks. It does seem to
me that the development of any molecule or any procedure is costly,
extensive—10 years or more—and if the pharmaceutical
industry is going to be charged for that then that is going to
slow things down enormously. The network situation is going to
help cure that, is it? Is it going to encourage pharmaceutical
companies to come forward with more new molecules and new procedures
than they would have done?
Professor Fentem:
I think the question is how do we best engage them in the discussions?
We are not at a stage yet where we can see clearly how that will
be managed. Clearly, we have made a rather unsteady start to this
because whereas the Government has made £100 million available
for the next batch of research networks, the money that was discussed
that would come from the OST to the MRC to support the research
on those networks has not yet been forthcoming. So we may end
up, on the present information, with networks but not with the
funding for research programmes. A rescue bid could come from
organisations like the pharmaceutical companies, obviously, and
so we perhaps do need to work out exactly how we will engage with
companies in organising the networks. These would be contracts,
in the end, not with individual academic departments but with
a network of departments.
Professor Weissberg:
Can I just come in on that? It is an extraordinarily complex interaction
between industry and academic and NHS research because, inevitably,
industry has a particular agenda, and that is that they want to
sell their product, and they want to protect their product. One
of the difficulties in trying to do research with industry—and
I think it has been well-exemplified recently—is they are
very nervous of you trying to do research on one of their products
that they do not currently have a licence for, not because they
are concerned that if you find that it works they are not going
to make a lot of money (they would do) but because they are concerned
that if you find something negative (and a good example of that
is the inhibitors that were being trialled for bowel cancer and
in so doing was the final nail in the coffin for their risk of
causing heart disease) it makes industry very nervous of doing
any further research, particularly outside their narrow remit
if their product is selling well. So it is very difficult to persuade
them to think laterally, if you like, with any of the products
they have out there. I think we have to recognise that we do need
to work with industry. They need us and we need them; it is a
matter of coming up with a framework in which we are all comfortable.
We are all, as researchers, a little bit nervous at the moment,
under the current framework—which is not really a framework
on how to interact with industry—as to how we will be perceived
in terms of our interaction with that company. So there is a lot
of work to be done to try to work out some ground rules there
that are mutually satisfactory, but certainly industry needs us.
I am sure it is no accident that the money for clinical research
in this country has gone up after industry was saying "We
cannot do clinical research in the UK and we will have to take
it elsewhere." They recognise the need to do clinical research,
preferably here, and we recognise the need for them to help us
do it. It is a matter of coming up with a framework we are all
comfortable with.
Chairman: We have,
effectively, run out of time, and I am concerned that there might
be a division bell ringing, in which case several Members of the
Committee would have to go, but I would like to get two more questions
on the table, perhaps, from Lord May and Lord Mitchell, with responses
from Professor Lees—and if you wanted to amplify them thereafter
that would be possible.
Lord May of Oxford:
Very quickly, we have been talking about the current recent past—and
may I say I completely agree that the research assessment exercise
is in more ways than one inhibitory of collaborative research,
and let us hope that that is one of the things that might be ameliorated—but
looking beyond that, what are the things that you see if you look
10, 15, 20, 25 years ahead? What are the things that you may care
to speculate on very briefly now, perhaps, that we might be looking
forward to? In particular, you have touched on stem cells earlier
but I wonder what you think might be some of the longer term promises,
given some of the things that have happened very recently.
Chairman: I wonder
if we could have Lord Mitchell's question, and then perhaps you
might make one response.
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