APPENDIX 14
Memorandum submitted by Marie Curie Cancer
Care
INTRODUCTION
1. Marie Curie Cancer Care (MCCC) was established
in 1948 "to attack and allay the disease of cancer".
The Charity is dedicated to the care of people affected by cancer
and the enhancement of their quality of life, through its Caring
Services, Cancer Research and Education. In 1999 it provided a
total of £34 million to support its unique nation-wide community
nursing service, the in-patient and out-patient specialist palliative
care in its Centres, professional education and research. It has
recently established the Marie Curie Palliative Care Research
and Development Unit at the Royal Free and University College
Medical School.
2. The Charity supports the Marie Curie
Research Institute based at Oxted in Surrey. The laboratories
serve two complementary functions:
2.1 To conduct a co-ordinated and peer reviewed
programme of research into the mechanisms responsible for cancer
using the latest molecular technology. It conducts a quality programme
of curiosity-driven research into fundamental aspects of cellular
behaviour, with low overhead costs and extensive international
collaboration.
2.2 To exploit the results of fundamental
enquiry for the development of new and improved methods for the
prevention, early detection, diagnosis and treatment of cancer
by collaborating in the downstream development of drugs, reagents
and methods with the pharmaceutical and biotechnology industries.
In addition to the basic research programme, there is now a scheme
for the development of translational research, for the rapid,
cost-effective implementation of laboratory results in addressing
specific clinical problems.
3. Since MCRI is a relatively small organisation,
considerable effort has been expended to ensure that its research
programme is nationally and internationally collaborative, is
highly focused and is cost-effective and is committed to bridging
the gap between laboratory and clinic. It is this context that
provides the relevance of this memorandum to the Committee's inquiry.
BASIC RESEARCH
4. The relevance of basic science to the
cancer problem cannot be assessed a priori. It is the results
that have relevance and not the intention. Ten years ago, some
of the most significant advances in our understanding of cancer
were emerging, for example, from studies of yeast genetics. Most
observers would not have recognised this work as cancer research.
It was good science whose impact emerged from the results.
5. The conduct of basic research is already
co-ordinated and informally controlled by a network of existing
ad hoc mechanisms. Collaboration is intense, especially internationally.
The various peer review processes, (and the quinquennial RAE)
although far from perfect, provide quality control of the science
and of the publications which result from it. The overall UK contribution
to basic science is of high quality. Britain remains a world-leader
in molecular biology, genomics and many aspects of cell biology.
Research takes place in a variety of settings, funded from a variety
of sources. This diversity is a strength, especially in determining
spending priorities. The collegiality of UK scientists, as well
as the peer review process, ensure that unnecessary duplication
of effort is avoided and that collaborative working is optimised.
This could be further facilitated, for example, by a world-wide
database of ongoing research projects.
6. Four comments may be worth making:
6.1 Cancer research is funded primarily
by charities and not by government. This is a curious reflection
on government priorities. And it leads to uncertainty of funding.
Charitable giving is in decline and most of the UK's cancer charities
are subject to unpredictable fluctuations in their annual commitment
to research. The largest of the medical research charities, The
Wellcome Trust, specifically excludes cancer research from its
portfolio.
6.2 Such funding as the Government does
provide is not equitably allocated. Research scientists working
in laboratories owned by charities have been specifically denied
access to responsive-mode Research Council grants. In our view
this is unjustified. Access to such funding is keenly competitive
and should be based on quality alone, not on the location or ownership
of the laboratory.
6.3 The intellectual curiosity of talented
individuals is unlikely to be enhanced by subsuming their work
into a broad portfolio. A national cancer institute, whatever
its format, would be almost certain to subordinate scientists
to managers with consequent damage to originality of thought.
6.4 A potential barrier to progress of the
UK cancer research base is the very high cost of some technologies.
Not every laboratory or institute has easy and open access to
a range of intermittently used but expensive equipment and methods,
eg time-of-flight mass spectrometry; atomic force miscroscopy;
facilities for the large-scale growth of cells or organisms; large-scale
animal facilities. The cost-effectiveness and productivity of
British cancer research could be significantly enhanced by mechanisms
designed to provide easy and open access to such resources. The
objective should be "joined-up cancer research", not
monolithic management.
TRANSLATIONAL RESEARCH
7. The transition from basic science into
the translational phase is not easily accomplished. Research results
do not leap out of the laboratory and into the clinic. They can
so easily moulder in lab notebooks or remain unregarded on the
shelves of libraries. The early stages of translational research
need careful nurturing. There is a range of tactics available
for technology transfer but they seem to operate in a piecemeal
fashion. To take the often unanticipated results from the fundamental
research laboratory and exploit them as rapidly and efficiently
as possible for the potential benefit of cancer patients is not
easily achieved. Indeed, it is our contention that translational
cancer research in the UK has many weaknesses. Firstly there need
to be effective mechanisms for recognising and reacting to significant
and exploitable data. Basic scientists are not necessarily best
equipped for this task.
8. Intellectual Property Protection. Where
original data can be protected under patent law the use of regular
surveys by IP reviewers can allow the identification and subsequent
exploitation of significant "inventions". This protection
is also important for safeguarding the value of the "inventions"
to other interested parties whose investment is necessary for
the effective translation of the original findings into exploitable
IP (eg the pharmaceutical industry). Formalised systems for effective
IP recognition and protection associated with mechanisms for subsequent
technology transfer are in use in some centres. The quality and
quantity of these services is variable from centre to centre.
It is also an expensive process. The cost of processing a patent
application through a three year cycle can be well over £30,000.
A laboratory-based scientist may be reluctant to lose such a sum
from his/her research budget for a single patent. The majority
of patents in the biological sciences are not taken up and do
not provide any revenue return. It is a form of investment which
is seen as a speculative luxury by many basic scientists. Indeed
the amount of "valuable" IP available for exploitation
is remarkably small.
9. Translational Research without IP Protection.
Many significant laboratory-based discoveries may not be amenable
to patenting and yet be capable of having a significant impact
on clinical practice. This is probably most relevant to diagnostic
methods, especially when a new application of an observation that
is already well described in the published literature. Identifying
sources of funding to carry out such work can often be problematic
and connecting the basic science to its potential application
may require specially trained entrepreneurs.
10. The Management of Translational Research.
It is important to recognise that translational research whose
function is to bridge the celebrated gap between laboratory and
clinic, differs from basic science. It requires a different style
of management. It is possible to write a business plan for a translational
project, to identify specific milestones and to lay out carefully
costed and timed plans. (To attempt such a management style in
basic curiosity-driven science would be futile).
11. The Location of Translational Research.
Experience obtained in these laboratories (MCRI) strongly supports
the idea that the early phases of translational research are most
effectively conducted alongside the basic science from which it
emerged. It benefits considerably from the continued interest
and support of the original discoverer, especially at the "proof
of principle" stages. There is often a two-way beneficial
effect, both on science and on morale. However, the evolution
of a translational project will eventually and inevitably carry
it away from the original basic science laboratories. This is
especially so when large-scale in vivo testing for effectiveness
and safety are needed or when scaling-up pre-production becomes
mandatory. At this stage a different environment is required,
a commercial and industrial setting such as a biotechnology or
pharmaceutical company. This will also be associated with a move
towards the clinic. This requires the involvement of well supported
clinical research centres, a suitable setting for Phase I (and
further) clinical studies.
PRECLINICAL AND
CLINICAL RESEARCH
12. The long overdue emphasis on evidence-based
medicine is very welcome but it begs the question of the UK's
contribution to such evidence. On paper the National Health Service
could provide an excellent environment for the conduct of all
forms of pre-clinical research. It does not. A significant weakness
in UK cancer research seems to lie in the pre-clinical and clinical
sciences, in bringing the results of translational research swiftly
and effectively to the bedside. This is where the development
of national cancer resources could play an important role by bringing
together patients and clinical scientists into well resourced
centres of excellence. As a focus for advanced translational,
pre-clinical and early phase clinical research such centres could
play an important role in accelerating the transfer of research
findings to the clinic. Effective mechanisms for brokering IP
protection and technology transfer could provide a powerful magnet
for big Pharma, the biotech companies and for the cancer charities
to collaborate in accelerating the application of research findings
for the benefit of cancer patients.
13. However, the conduct of high quality
clinical cancer research cannot take place without a strong and
well supported infrastructure of cancer services. Pre-clinical
and early stage (eg Phase 1) studies require extensive resources
and laboratory support in well-funded centres of research excellence.
Later stages in the process, especially the conduct of controlled
clinical trials, requires access to very large numbers of patients
from all over the UK. The cancer services required to support
the effective conduct of such trials are not generally and equally
available across the UK.
14. The effective delivery of high quality
evidence-based care to every cancer patient in the UK is an essential
pre-requisite to provide the base on which to build an effective
programme of clinical research. Furthermore, it is imperative
that all administrators and trust officials are "research"
friendly. It is important to realise that the practice of clinical
medicine is (or should be) in itself a research activity. In
an ideal world all cancer patients should be treated in the setting
of a clinical trial. This requires more public understanding of
the benefits of clinical trials, and a more concerted effort to
engage the support of patients. There are very few circumstances
in which the treatment of a given patient can be regarded as optimal
or routine. There is always room and need for improvement. We
will leave others to comment on such matters as the career structures
of clinical oncologists and the role of clinical research in that
training, as well as the application of NHS R and D funds to clinical
cancer research.
15. It is difficult to see how a nation-wide
programme of clinical research could be encompassed in a single
"National" Cancer Institute. Furthermore there would
seem to be little benefit in attempting to centralise the fundamental
science base in one centre, nor the translational projects emerging
therefrom. Those of us with long memories will recall the abortive
attempts to establish a Clinical research Centre some 30 years
ago. Its failure offers some lessons.
16. Co-ordination and joint-working in these
small islands does not necessarily rely on geographical location.
But some aspects of joined-up cancer research such as the feeding
through from the translational phase to the pre-clinical could
be significantly enhanced by ensuring that these activities are
clustered around regional clinical cancer centres. The distribution
of the current centres of clinical and research excellence across
the UK provide a framework for the development of a network of
collaborating organisations. Such collaborations would be facilitated
and enhanced by the sharing of high-cost technological resources,
by electronic communication associated with the establishment
of easy access to UK wide databases of resources and ongoing projects,
banks of clinical material such as tumour and normal tissue samples
as well as anonymised clinical data. Furthermore rapid publication
of all research data on line should be encouraged. The recent
introduction of the PubMed Ceontrol website in the US and the
proposed E-BioSci European initiative provide possible models
for the rapid communication of research results.
17. Given the will of the participants and
the appropriate enabling infrastructure (hardware, software and
people) a "Virtual" Cancer Institute could be developed
to act as a catalyst for joining-up (and consequently, speeding-up)
contributions from a range of nation-wide resources to forge a
more cohesive programme of co-ordinated cancer research in the
UK.
CONCLUSIONS
18. The conclusions from this analysis are
summarised in para five of the Executive Summary.
6 March 2000
EXECUTIVE SUMMARY
INTRODUCTION
1. Marie Curie Cancer Care runs a Research Institute
at Oxted which is small, cost-effective, and engaged in extensive
international co-operation. It seeks to deliver excellence in
basic research and also to exploit the results for the development
of improved methods for prevention, early detection, diagnosis
and treatment of cancer. It is important to distinguish between
curiosity-driven basic science; translational research and clinical
research. Each requires distinct styles of management and the
boundaries between them are perhaps the weakest area of British
cancer research.
BASIC RESEARCH
2. The overall contribution to basic science
is of high quality. But:
2.1 Cancer research is principally funded
by charities rather than by government. This is odd. Cancer charities
are subject to unpredictable fluctuations in their annual resources
which may impede long term strategic developments.
2.2 Charity-run laboratories are specifically
excluded from responsive-mode Research Council grants. This is
unjustified.
2.3 The quality of curiosity-driven basic
science would be damaged rather than enhanced by incorporation
into a National Cancer Institute.
2.4 But the cost-effectiveness and productivity
of UK cancer research could be significantly enhanced by mechanisms
designed to provide easy access to a variety of intermittently
used but expensive equipment.
TRANSLATIONAL RESEARCH
3. The early stages of translational research
need careful nurturing and basic scientists are not necessarily
best equipped for this task:
3.1 There needs to be more streamlined and
cost-effective mechanisms to identify and protect intellectual
property.
3.2 Translational research can be conducted
without IP protection but it is difficult to identify sources
of funding.
3.3 The conduct of translational research
requires an entirely different management style from that necessary
for the facilitation of basic science.
3.4 The early phases of translational research
are most effectively conducted alongside the basic science from
which it emerged. But there will come a time when it needs a different
environment, nearer the clinic or in a commercial and industrial
setting such as a biotechnology or pharmaceutical company.
PRE-CLINICAL
AND CLINICAL
RESEARCH
4.1 The current oncology centres across
the UK should be encouraged to become Regional Cancer Institutes
with collaboration facilitated by the UK-wide on-line publication
of data, project data-bases etc. Joint working with the Biotech
and Big Pharma sectors should be encouraged by streamlined and
co-ordinated technology transfer mechanisms.
4.2 Controlled and properly funded clinical
trials are needed on a nation-wide basis, in better and more equitably
distributed clinical cancer centres. A research-friendly environment
is essential and the treatment of cancer patients should be managed
in the context of controlled clinical trials as a matter of routine.
CONCLUSIONS
5. The following conclusions emerge from
this analysis:
5.1 UK laboratory-based cancer research
is of high quality but needs more financial support and more equitable
distribution of government funding.
5.2 There is a need to streamline and co-ordinate
resources designed to enhance joint working, rapid data access,
I.P. protection and technology transfer.
5.3 Early phase translational research at
basic science centres across the UK should be encouraged both
financially and managerially. Later phases require an industrial
environment and access to patients, clinical material and clinical
data.
5.4 None of these objectives would be met
by a bricks and mortar National Cancer Institute, which would
drain scarce resources from the rest of the Nation's cancer research
activities. The collegiality of electronic media could achieve
considerably more cost-effective joint working than expensive
architecture.
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