Examination of Witnesses (Questions 426
- 439)
WEDNESDAY 17 MAY 2000
PROFESSOR KAROL
SIKORA, PROFESSOR
SIR RICHARD
PETO FRS AND
PROFESSOR BRUCE
PONDER
Chairman
426. Professor Ponder, Professor Sikora, thank
you very much indeed for coming before the Science and Technology
Committee this afternoon. We hope that we shall be joined shortly
by Professor Peto who I believe is having some delay in his travel
arrangements. We have a variety of questions to put to you this
afternoon and we will try to direct them as far as we can because
if we ask each one of you to answer every question we put we shall
never get through the long list of questions we have. If we do
direct a question, for example, to Professor Sikora and Professor
Ponder wishes to make a comment, we shall be pleased to hear it,
but we would also be pleased if every question was not answered
three times; otherwise we shall not get through our agenda. Would
you both please introduce yourselves so that it is written into
the record?
(Professor Ponder) I am Professor Bruce
Ponder. I am Professor of Oncology in the University of Cambridge.
(Professor Sikora) I am Karol Sikora. I was Professor
of Oncology at Hammersmith and am now Vice-President for Cancer
Research at Pharmacia Corporation.
427. Thank you very much indeed. Professor Ponder,
what are the main areas of research at the present time that will
lead to the next generation of patients getting better cancer
treatment than they get now?
(Professor Ponder) First of all, thinking about the
development of new treatments, I suppose a rational approach to
that depends on our understanding the critical differences between
cancer cells and normal cells, and I think that the approach to
that is through better understanding of the cellular and molecular
biology of the normal cell, how it is disturbed in cancer, and
particular areas which look promising at the moment are topics
such as signal transduction, that is, the controlling mechanisms
of the cell, mechanisms controlling cell death, mechanisms controlling
DNA repair. It would be very rash to predict which of those is
going to provide the answers; maybe several of them will provide
different answers in different cancers. Although we obviously
focus a lot on the development of new treatments we should not
neglect other possibilities of research. In particular I think
there is quite a lot of scope in the short term for improving
the efficacy of the treatments that we have already, using them
better. One way of doing that is to be able to describe tumours
more precisely in terms of the molecular defects within them and
match those to the treatment. I think there is potential still
for screening and prevention and the areas of research which are
important there are epidemiology, the genetics of susceptibility
and gene environment interactions, and understanding of the preneoplastic
process, that is, the changes which are occurring before the cell
finally becomes a cancer cell.
428. You have mentioned several potential treatments
there. Do you think that in the United Kingdom we are trying to
tackle too many treatments at the same time and we would be better
if we specialised in one or two?
(Professor Ponder) Too many areas of research?
429. Yes.
(Professor Ponder) No, I do not think so. Obviously
there is merit in focus and the Grants Committees always want
people to focus but I do not think we have the wisdom to know
what to focus on. Your question has overtones, if it is carried
through logically, of direction of research by the Committee and
I think that is generally not a good direction to go in. My own
view is that the researcher should come up with the ideas and
the good ideas will win out and attract the resources and I would
be reluctant to see a centralised curtailing of the scope of research.
430. Before I put my question to Professor Sikora
may I welcome Professor Peto and say to him how pleased we are
that he has come along this afternoon. We know the difficulty
he has had with his travel arrangements and we thank him for letting
us know that he might be a minute or two late. Before we resume
our questioning perhaps I can invite you, as I did our other two
witnesses, to introduce yourself for the sake of the record, Professor
Peto.
(Professor Sir Richard Peto) My name is Richard Peto.
I have been a cancer epidemiologist and cancer trials statistician
for the last 30 years, looking at the large scale patterns of
the effects of smoking and the effects of particular treatments
in cancer.
431. Thank you very much indeed. I am going
to turn to Professor Sikora and perhaps when Dr Gibson asks his
question and Professor Peto has got his breath back we might include
him in the dialogue. Professor Sikora, did you agree with the
answers given by Professor Ponder and, if not, what different
answer would you like to give?
(Professor Sikora) No. I think it is a fairly common
theme. Most of us in oncology believe that the way forward is
less surgery, much greater conservation with surgery, some tinkering
with radiotherapy in terms of better conformation of radiotherapy
based on computer technology advancing dramatically, but the real
future is in selective systemic treatments that go right round
the body. Cancer is often a systemic disease. Even what we call
early breast cancer is not really early cancer. It is in fact
quite late because the disease has already metastasized and that
is the cause of the problem, why people die from the disease.
We believe that the future in the near term is about understanding
more about targeting the right drugs, some of which we have already,
to the right patients, but over the next five to 10 years uncovering
completely new models of very selective drugs based on the sort
of approach that Professor Ponder mentioned, signal transduction
pathways which have now been uncovered, and already very sophisticated
methods using genomics have been developed to try and yield more
drugs. I think the main stumbling block internationally in getting
progress with these new drugs is the sheer number of molecules
that will be available for general study and how to sort out from
this molecular soup if you like which ones to pick and take on
and do the long term studies on. The other problems are going
to be that many of these molecules will not cause tumour regression
necessarily. Patients may have X-ray changes of cancer in the
lung and they will remain there. The disease will be held controlled
if you like. To get data on whether these drugs are actually beneficial
will take a lot longer. There is a lot of emphasis that will have
to go right at the beginning of clinical research to try and work
out whether these drugs really affect the target we think they
are affecting. That will give you, if you are in the industry,
the commercial ability to persuade those that are investing in
any company to pay for the large scale trials. We would want to
have that validation at an early stage. That is the missing link
at the moment.
432. I think we all know that cancer treatment
and eventually cancer cure is a continuum but the newspapers will
always have it that there is going to be a breakthrough, or indeed
there is a breakthrough. As scientists, each and every one of
us on this Committee, we know something of the research and we
know that very seldom in life do you get breakthroughs, and even
a breakthrough is just a bigger part of the continuum. Do you
believe in breakthroughs in cancer treatment or do you think it
will just be greater emphasis on the continual work that will
lead to better treatment as a combination of all the past work
that has been done?
(Professor Sikora) When one is in cancer therapy,
looking back at 25 years of it, one does not perceive breakthroughs.
There have been ideas that have led to something but they are
not really breakthroughs in that sense. I do not think there will
be a single unified hypothesis, a single drug, that in 2006 will
revolutionise the treatment of cancer. Rather it will be a series
of changes, gradual improvements, gradually understanding the
profile of a cancer, how to select the right agents to control
it, and that will take us forward. There will not be a year in
10 years' time when we say we have made a radical change.
Dr Gibson: Jim Watson was over here yesterday
talking to some of us in another Committee and he said that we
know enough now about the processes in terms of what you are talking
about and we should get on and do it. Why does it take so long
to get from the bench as it were to the bedside?
Chairman: I am going to have to suspend this
Committee now by Standing Orders. I should suspend for 15 minutes
but I am going to try and suspend for six or seven minutes if
Members could try and get back quickly. I do apologise to our
three eminent witnesses for the delay during that period of time.
"The Committee suspended from 4.25 p.m.
to4.31 p.m. for a division in the House."
Chairman: We will resume. Dr Gibson is not back
yet so we will go to Dr Turner and return to Dr Gibson on his
return.
Dr Turner
433. This is a question probably on which the
views of all of you would be welcome. Funding of cancer research
in the United Kingdom comes principally from non-government sources,
unlike other research areas. It comes mostly from charity and
industry. Do you believe that the Government is doing enough in
funding cancer research? Do you think that it is sitting back
and expecting industry and the cancer charities to make up for
the state's deficiencies in this area?
(Professor Sir Richard Peto) I think if you say, "Would
it be nice to have some more money?", everybody is always
going to say yes. If you say, "Would the money be better
spent on cancer research than on education or on various other
things?", I do not know. It is not clear to me that the balance
is as grossly wrong as it is sometimes portrayed as being. Certainly
there are things that could be done with more money. That is obviously
always going to be the case. But if you are asking a question
like that then you have to compare it with something. Otherwise
I do not think any sensible answer can be made. I would like to
make one further point, which is that I am concerned that there
is a mis-perception that Britain is doing extremely badly in the
treatment of cancer and that the survival rates are very much
worse here than elsewhere. It is not clear to me the extent to
which this is true. This may in turn lead to distorted priorities.
The comparison of survival rates between different populations
is not a reliable way of determining whether treatment is being
given better in one population than in another because the survival
rates are dominated by artefacts of the thoroughness with which
one counts cancers, with which the incidence of cancer is monitored,
and the thoroughness with which one should recognise somebody
as having cancer and you then follow up and find out whether they
have died or not. The international comparisons, the comparisons
from one time period to another within this country, based on
the recorded survival rates, are actually rather misleading. In
some respects I think that this country has done remarkably well.
For example, in breast cancer we have had the best decrease in
breast cancer mortality of any country in the world over the last
10 years. The overall breast cancer death rate in middle-aged
women in this country is down 30 per cent on what it was 10 years
ago, and yet to read the newspapers you would think that we were
completely dismal in the treatment of breast cancer. We have actually
had a better improvement than any other country in the world.
Chairman
434. Professor Ponder, would you care to add
anything to that?
(Professor Ponder) If I may, yes. Leaving aside the
question of whether money would be better spent on cancer or on
some other disease, from the perspective of somebody who is trying
to set up a new cancer unit in Cambridge which is focusing on
translational research, I think my answer would be that the funding
bodies such as the charities, the Cancer Research Campaign and
the Government bodies such as the MRC provide money which is very
largely for specific research projects, but to carry out these
projects effectively, particularly in the clinical area, you need
quite a lot of infra-structure. To do translational research in
Cambridge we need to be able to collect information about our
patients across the whole hospital; we need to collect the material.
If I manage to get funding for clinical researchers their activity
will lead to a need for more pharmacists, more pathologists, more
radiologists, more surgeons. It is of some use (although limited)
the CRC or the MRC giving me a project or a programme grant, because
I cannot deploy this money to the best effect because I do not
have the infrastructure within the Health Service. That is what
is missing and there is nobody who seems to regard it as their
responsibility to do something about this. You might think that
the NHS are supposed to address this. I am told that my own department
in Cambridge receives £400,000 a year in allocation from
the NHS R&D but there is not a single pound of that the direction
of which I am able to influence, so it is of no use to me in addressing
these problems. That I see as the major missing role if you like
of government funding in making cancer research effective.
(Professor Sikora) I think there are two things. First
of all, the cancer survival, which is a very contentious topic,
and I would disagree with my colleague on the right, and say that
Britain still lags behind mainly because if you look at other
objective factors such as the number of trials in oncology, drug
spend, radiotherapy growth, everything is well below European
averages. But that is not really the issue for this Committee
in cancer research. What Professor Ponder has said is the key.
The infrastructure is very poor, patchy and depends on individual
personalities striving to build something and therefore creating
something in a centre that you can then invest in. The problem
for the pharmaceutical industry now is that the difficulty is
that you need to have some large academic centres for early phase
drug development where you can measure in a few patients very
precisely what is going on. After that you want to have large
populations where you can do studies of treatment. Central Europe
and the Pacific Rim countries have drastically improved their
medical infrastructure and because cancer drug development is
very much aimed at the American market—60 per cent of cancer
drugs are actually prescribed for four per cent of the world's
population—the United States population, it means that once
the FDA, the Food and Drug Administration in Washington, agrees
to take data from Central Europe and the Pacific Rim (which they
now have), these countries become very fertile places to do clinical
trials simply because the costs are about a fifth of doing them
in Britain. To compete we have to build up the infrastructure
both of early phase drug development and the infrastructure of
proper drug development. Having seen how the Department of Health
R&D funds are distributed I too at Hammersmith had a budget
that I could not get hold of. I could not change it round. I was
told that 20 per cent of my salary came from this.
Chairman: Dr Turner, could I now ask you if
you would direct your question to one member of our witnesses
because we are not going to get through our agenda.
Dr Turner
435. Professor Ponder or Professor Sikora could
answer the next follow-up. It seems to be clear then that the
nature of the present funding system is distorting the research
agenda because you are unable to pursue a lot of the individual
activities that you would like to. Is that fair?
(Professor Ponder) Yes. I am not sure I would use
the word "agenda". It is distorting the effectiveness
of the use of the money.
436. Do you think the MRC, in supporting these
areas of research, is operating in a way that is going to fund
and deliver successful anti-cancer therapies and prevention strategies?
Has the MRC got its strategy right?
(Professor Sikora) I would say that the scale of investment
is so low at an international level that it is not worth doing
at the moment. Either you are in this business to try and succeed
and invest heavily in cancer development, both in prevention and
in large scale trials, or you do not do it. What the NHS has is
a remarkable system up and down the country, with a population
of 57 million, 180,000 people with cancer, and yet there is no
systematic approach to try and get patients into clinical trials.
American HMOs, health maintenance organisations, which represent
a sort of mini-NHS for the populations that go to these plans,
have already appointed clinical trials teams for cancer to provide
the infrastructure so that a consultant in Cambridge, for example,
does not have to worry about the extra workload of entering a
patient into a clinical study. The infrastructure to do that is
provided for and managed properly and so all the data sheets,
the relatively boring studies that are required to validate the
clinical trial, are looked after for the person. The sort of problem
Professor Ponder has with the infrastructure is taken care of.
We do not have that privilege in the United Kingdom; I do not
think we ever have had. That again leads to personal effort, slush
funds, all these sorts of things, being used to try and support
the struggle. In some places it works; in other places it does
not. Of course there is a dynamic. As people change some places
peak and then go down but that should not be the case in a country
like this.
Dr Turner
437. It would be fair to say then, would it,
that there are promising research areas which are being neglected
because the Government is not having a sufficient influence on
the research agenda, particularly in terms of properly funding
it? Can you expand on that and give some specific examples?
(Professor Sikora) As we go through the next three
years there are going to be a remarkable number of compounds coming
into the clinical trial arena that Britain will not be part of
because there is not the infrastructure to do it. There are physicians
that would be interested in doing the trials, there are patients
with cancer that certainly would like to be part of the clinical
trial, but it will not be possible at the moment because there
just is not the infrastructure to get things going. Information
technology, which Professor Ponder has mentioned, is fairly poor
and does not link up to things in this country. We are moving
into an era where validated clinical trials are monitored electronically
in real time by the pharmaceutical industry and by the regulators,
both the FDA and the European regulator in London. Getting to
that point requires a different mind-set of infrastructure and
that is perhaps what I see as the biggest lack in terms of the
Government funding for cancer research in this country. It has
never been properly addressed by the MRC. They have a clinical
trials committee but if you look at the structure of what they
are doing it is not providing an infrastructure. It may help a
little bit with the statistical analysis but it is relatively
small scale.
(Professor Ponder) Could I add something very briefly
to that? It is an anecdote, I suppose, just one example also of
how the lack of infrastructure prevents us from carrying through
when we have discovered something. In 1993 we identified a gene
which predisposes to a particular fairly uncommon form of inherited
thyroid cancer. What was particular about this was that it was
one of the few inherited cancers where you can show unequivocally
that having a gene test for this condition predictively is of
value, and six years later the National Health Service still does
not provide a complete genetic testing service for the mutations
in this gene, nor is there a national register which allows us
to keep track of family members so that children and their parents
can be offered advice and the opportunity for screening, nor is
there any mechanism in place for us to evaluate the most efficient
way to use the genetic testing. This is not for want of trying.
There have been committees: the Harper Committee has recommended
about this. We just cannot make it happen.
Dr Gibson
438. Do you think the Department might have
costed it up and found it was too much? Are you cynical about
that?
(Professor Ponder) There are orphan diseases which
drug companies are not interested in and maybe there are orphan
diseases which governments are not interested in and I suppose
that is possible. I am not aware that such an exercise has been
carried out. I would ascribe it to the inertia of the system or
the impenetrability of the system rather than to any positive
decision.
439. But you describe it as a minor cancer when
there are major ones where, as Professor Sikora says, we have
inroads to make in some of them. We have done well in some but
not in others. Maybe the Government is right to take out the major
cancer killers.
(Professor Ponder) Maybe. I use this as an example
though. I think you could multiply that example for more common
conditions. It happens to be one which is close to my heart because
I was involved in it but it is still 50 people a year who are
getting a very nasty disease, some of which could be prevented.
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