APPENDIX 37
Memorandum submitted by Professor A G
Dalgleish, St George's Hospital Medical School
INTRODUCTION
I am Angus George Dalgleish, the Foundation Professor
of Oncology at St George's Hospital Medical School and the Visiting
Professor of Oncology at the Institute of Cancer Research. I am
a UCH graduate and have served in several different hospitals
in Australia, including the Queensland Radium Institute at the
Royal Brisbane Hospital and the Royal North Shore and Royal Prince
Alfred Hospitals in Sydney and the UK where I have had clinical
appointments at the Royal Marsden Hospital, Hammersmith Hospital,
including Northwick Park and the Royal London Hospital. My current
hospital, St George's Hospital, runs a large number of ongoing
trials into cancer treatment including two FDA audited studies
financed by the National Cancer Institute, USA.
My own laboratory research has already led to
new trials in the clinic, including an original vaccine for prostate
cancer which has already recruited sixty patients and a unique
drug combination for pancreatic cancer. We have also been selected
for Phase I/II studies for Thalidomide analogues in the treatment
of cancer.
SUMMARY
Cancer research is poorly funded in the UK,
especially with regards to clinical research. A major improvement
in the ability to perform good clinical research and increase
the care to patients could be made by putting in research nurses
and data managers into every major oncology centre to provide
the infrastructure to perform trials. In the UK the concept of
a national cancer institute may work better as a virtual institute
with clinical trial centres in the major regions. Some of the
most productive clinical research is not drug company funded but
doctor driven and the whole ethos of this is under threat from
the EEC directive which needs strong opposition. Good cancer research
with clinical application suffers from the fact that current structure
and resources are grossly deficient and that only a significant
improvement in budgets of approximately two fold could make a
serious impact on patients with cancer which is likely to be one
in two of the population in the next ten years.
CANCER RESEARCH
PRE CLINICAL,
CLINICAL AND
DRUG COMPANY
TRIALS
1. It is important to realise that there
are two types of cancer research in the UK, being that which is
funded by drug companies for enrolling patients in a clinical
trial to obtain registration and the rest. At most cancer centres
the majority of cancer research is drug company given, usually
providing a significant sum, plus the free treatment for every
patient enrolled (depending on the study, sums between £3,000
and £6,000 are not uncommon.) Cancer research in hospitals
is usually funded by the ICRF or the Cancer Research Campaign.
ICRF funds its own units and does not offer funds for competitive
bids. The CRC also runs its own units and is the only funding
organisation that funds research outside one of its main centres.
Unfortunately, the amounts are not significant enough to be able
to fund any basic clinical cancer research. More recently the
Leukaemia Research Fund has become a significant player in funding
clinical work and trials in the treatment of leukaemia and myeloma.
The MRC funds relatively little trial work directly due to the
existence of the two main cancer charities, although it does offer
a good co-ordinating role for clinical trials. The Wellcome Trust
also does not fund clinical cancer research although it has indicated
that it may be less stringent about this in future. The EEC funds
meetings, travel and exchange of people and materials. It is my
experience that if one is not supported as a centre or group by
one of the two major charities that it is extremely difficult
to fund cancer research in the UK and that the realisation that
this is the case has led a number of influential individuals to
start charities, often successful, which are targeted at one particular
problem such as the Breakthrough Charity for breast cancer and
the Prostate Cancer Charitable Trust. My own work is in the field
of designing cancer vaccines as treatment for cancer and this
could never have got started if it was not for the generosity
of private individuals donating to a charity called the Cancer
Vaccine Campaign here at St George's.
CLINICAL TRIALS
AND INFRASTRUCTURE
2. In the field of hospital/clinical based
cancer research it is estimated that less than 5 per cent of cancer
patients go on trials. Patients who go on trials do better than
others who don't, even if they get no active treatment, presumably
due to the regular monitoring and support. In my opinion the most
important thing to correct in the British hospital system is to
provide oncology centres with the infrastructure to do clinical
trials. This means providing a team of two research nurses and
a data manager with more positions being required for the very
busy centres. This would lead to the ability to target 30 per
cent to 50 per cent of patients for clinical trials. This means
more rapid assessment of treatment as well as the potential savings
that is never taken into account under the bizarre accounting
systems of current Trusts and that is that most patients on trials
will get their drugs free. If there is not a trial available then
they will be prescribed a drug that the hospital has to pay for.
However, many drug trials may be lost in the future because of
the lack of appropriate infrastructure at most sites and the increasing
demands of hospital's investigators for fees for enrolling patients
into these studies. The big pharmaceutical companies have already
realised that is now cheaper to perform clinical trials in many
European countries than it is in the UK.
3. This infrastructure which is missing
at most of the non cancer charity supported centres would allow
a large number of other studies to be performed that are not necessarily
supported by drug companies. Such an infrastructure is obviously
necessary in order to take basic research into the clinic.
THREAT OF
CHANGE AND
EEC REGULATION
4. At the present time the clinical trial
system has two main approaches. The first is called a Clinical
Trial Exemption Certificate and is suitable for a drug company
sponsored trial. The other approach is called a Doctors' and Dentists'
Certificate and this is for clinical trials at the instigation
of the doctor or dentist and can use approaches which would not
normally meet the rigours of a major drug company product. For
instance my own work on different vaccines has gone through this
approach and without it there could be no development. We have
been warned that there is an EEC draft directive which would ban
this route of clinical trial circulating, meaning that in the
absence of a large company making the various vaccine preparations
to good manufacturing process (a process which increases all costs
by at least ten fold) this vital area of clinical research could
be outlawed. In this regard it is ironic that America has recently
gone the other way, not requiring the onerous restrictions of
GMP for vaccine development. If this EEC directive is passed all
such research will be confined to America with British and European
patients only gaining access after five to ten years when a successful
product has been registered.
5. I regard the existence of this directive
as one of the major barriers to taking basic research into the
clinic in the UK.
NATIONAL STANDARDS
AND A
UK NCI
6. The number and distribution centres of
Cancer Research should really reflect the geographical distribution
and the relevant population. It is clear from my own practice
which receives referrals from all over the country, that there
are enormous differences in the standard and expectations of patient
care and this should not occur if there really were accessible
cancer research centres nearby. There is a need for a UK National
Cancer Institute but the nature and siting of it are far from
clear. There is a strong case to be made for it being a virtual
institute as opposed to being sited in one building. There may
be more of a case for a number of regional clinical trial centres
under an NCI logo to be centrally funded. As a member of the Scientific
Advisory Council of the Edward Jenner Institute for Vaccine Research,
now sited at Compton in Berkshire, I have been made aware of extreme
criticism about the siting of this Institute at a time when vaccine
research clearly needs to be clinically driven. Another major
issue that would need to be considered in addressing a national
cancer institute or clinical trial centres is that current hospitals
who specialise in cancer with clinical trials are really driven
by private practice. Especially in London, this is driven by necessity
as the pay of the clinicians is so drastically poor compared with
colleagues in Europe and America and other professions here at
home. It is important to note that the big cancer research institutes
in the United States are all academically run and the private
practice factor is removed. However, they also pay realistic salaries.
(A similar position to my own in a USA university would pay at
least two and a half times my current salary).
THREAT OF
DRUG COMPANY
SPONSORED RESEARCH
DISAPPEARING
7. The issue in industrial development in
clinical trials of anti cancer agents is very pertinent. It is
likely that the money invested in the UK clinical trial structure
may disappear completely if the appalling low drug budget is not
increased by several fold. In short, the cost of performing clinical
trials and getting registration just for the current UK market
is prohibitive. Whereas we used to have a good reputation for
excellent clinical trials it is now clear that we offer no more
than many other countries who also agree to perform the studies
at a fraction of the cost. They are obviously quicker at realising
that this gives them access to free drug supplies than the current
NHS administration! It is clearly important to address both these
issues, namely the need for a national clinical trial research
infrastructure as well as provision of a budget to purchase new
cancer agents.
CLINICAL ONCOLOGY;
RESEARCH?
8. The brief talks to the value and status
of research amongst NHS clinical oncologist in the application
of such funds to clinical oncology. Whereas clinical oncologist
is a clinician who treats cancer it has a more specific meaning
professionally referring to radiotherapists. If this is the case,
it is perceived that research is not of a high priority amongst
radiotherapists. Indeed, there is a severe shortage of any academic
radiotherapy core and suitable candidates for chairs are very
hard to come by. However, there are a large number of trials involving
radiotherapy that could be addressed if the facilities were available.
With current waiting lists I suspect there is no time to entertain
these studies unless there is the provision of suitable equipment
and staffing which appears to be woefully inadequate even at the
best centres. I thing it is very important to look again at several
areas where radiotherapy is used.
Not only may it be possible to reduce the
amount of radiotherapy (and the number of radiotherapists trained)
in some circumstances but it may be possible to greatly enhance
the efficacy of radiotherapy combining it with other modalities.
We have noted a marked synergy between radiotherapy and patients
on immunotherapy. This association to my amazement was first
reported in 1962. In spite of enthusiasm from the radiotherapists
who are jointly at SGH and the Marsden, we have been unable to
get a research trial on this off the ground due to the lack of
capacity of the machines and the infrastructure. This mirrors
the problems of doing any reasonable simple innovative research
that might have a big impact that is not funded by a drug company.
CONCLUSION
9. In conclusion it is important to realise
that whatever particular issues have been raised, the bottom line
is that cancer research and the clinical extrapolation possible
improved by just changing management and communication in the
absence of significant increases in funding for cancer treatment.
At the current time the demand is approximately twice that can
reasonably be handled and by the time it is addressed it will
be more so anything less than a doubling of the resources it is
likely to be no more than ongoing first aid.
22 March 2000
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