Memorandum by Cancer Research UK (PI 59)
1. BACKGROUND:
CANCER RESEARCH
UK'S ROLE
IN DRUG
DEVELOPMENT
1.1 Cancer Research UK[3]
is the world's largest independent cancer research organisation,
with an annual research spend of over £213 million. Cancer
Research UK funds research into all aspects of cancer from exploratory
biology to clinical trials of novel and existing drugs as well
as population-based studies and prevention research.
1.2 Cancer Research UK recognises the high
level of capability and expertise within the pharmaceutical industry,
particularly in taking novel diagnostics and drugs to market.
Cancer Research UK works with the pharmaceutical industry where
such collaborations help us achieve our aims.
1.3 Cancer Research Technology Ltd is the
technology transfer arm of Cancer Research UK and is responsible
for most direct interactions with industry. Cancer Research Technology's
principal function is to facilitate the development of cancer
discoveries which could form the basis of new diagnostics, therapeutics,
or enabling technologies. Cancer Research Technology handles all
licensing and contractual relationships with pharmaceutical companies
arising from research funded by Cancer Research UK. All drugs,
diagnostics or research tools licensed to pharmaceutical companies
by Cancer Research Technology are issued on the condition that
the eventual marketed product is aimed at maximising patient benefit.
1.4 Cancer Research UK is Europe's major
non-commercial funder of research into drug innovation. We support
this research through project-based and long term funding. The
latter provision underpins our funding of specific clinical trials
by supporting areas such as exploratory biology and the development
of predictive biomarkers for drug efficacy and toxicity.
1.5 Cancer Research UK supports drug innovation
work through two main mechanisms.
1.5.1 Firstly, our in-house Drug Development
Office takes new drugs first into man[4].
The Drug Development Office and key Cancer Research UK clinical
centres have taken over 100 drugs into man for the first time.
Cancer Research UK has traditionally only taken these drugs to
a phase in development where they can be licensed out to the pharmaceutical
industry. Because of the cost and regulatory requirements we do
not conduct clinical trials aimed at gaining marketing authorisation.
1.5.2 Cancer Research UK has stringent procedures
to ensure the quality and clinical relevance of our early drug
development. Around 30-50% of the drugs that our Drug Development
Office takes into man for the first time are provided by biotechnology
companies. All proposals to take these drugs into clinical trials
are required to have detailed protocols, developed by the investigators
in collaboration with our Drug Development Office. These protocols
are then subject to international expert peer review and internal
review by Cancer Research UK's New Agents Committee. All trials
conducted in the UK are required to be scrutinised by independent
Research Ethics Committees. Cancer Research UK requires that all
results from trials are published. If the drug being tested has
been provided by industry then they will bear the full development
cost. In these instances Cancer Research Technology and Cancer
Research UK's Drug Development Office will ensure that appropriate
intellectual property rights are negotiated for the charity. In
return the company will benefit by having access to considerable
intellectual expertise across a wide range of disciplines (eg
clinical imaging) during the development process and the clinical
trials will be conducted in Cancer Research UK centres.
1.5.3 Our second mechanism for supporting
innovative drug research focuses on existing licensed drugs being
applied in novel ways, or on different types of cancer from the
one in which the drug was originally licensed. To support this,
Cancer Research UK and the Medical Research Council have created
the Clinical Trials Awards and Advisory Committee to peer-review
and fund trials that are then run through the National Cancer
Research Network. This body only considers trials for which the
primary aim is benefit to patients. All results from these trials
are scrutinised by an Independent Data Monitoring Committee, who
are the only body to see unblinded data. All results emerging
from trials approved by the Clinical Trials Awards and Advisory
Committee are published.
1.5.4 Pharmaceutical companies may support
the above trials in a number of different ways, from providing
free drugs, to fully funding some clinical trials. The key issue
for Cancer Research UK, irrespective of whether clinical trials
do or do not have any industry support, is that trials are all
judged by the same transparent mechanism including extensive international
peer-review, to judge the quality of the science and public benefit
of the proposed trial. Importantly, Cancer Research UK retains
control over the trial and the protocol as well as the data generated
to which there is unrestricted access for analysis.
2. QUESTION 1:
THE IMPACT
OF THE
PHARMACEUTICAL INDUSTRY
ON DRUG
INNOVATION
2.1 Pharmaceutical companies play a key
role in bringing innovative cancer drugs and diagnostics to market.
However, advances in oncology should not only be considered in
the context of individual drugs, but also the use of these drugs
in combination with other drugs, surgical techniques or radiotherapy.
We appreciate that for commercial or legal reasons it is often
difficult for the pharmaceutical industry to make drugs available
for clinical trials evaluating combinations of novel treatments.
Nevertheless, it is essential that the UK finds a way to overcome
this barrier for the best patient outcomes from both commercially
and publicly-funded research. The academic sector has a critical
role to play in evaluating novel treatment combinations, but may
require funding support from Government or the pharmaceutical
industry in order to do so.
2.2 The pharmaceutical industry has the
capacity to make a huge difference in drug innovation by further
investment in novel approaches to early drug development. This
could be achieved by greater partnership with not-for-profit research
organisations. The future success of the pharmaceutical industry
depends on taking new discoveries to the clinic, and we believe
a more flexible partnership with the academic community would
further enable such innovation[5].
Failure rates in taking cancer drugs to market are high (around
95%), due mainly to difficulties in demonstrating efficacy or
for safety reasons. This clearly demonstrates the need for better
experimental models, and for proof-of-principle trials to be performed
earlier in the development process to prove that the drug will
work according to expectation. These are both areas in which academia
has particular expertise.
2.3 As failure rates in drug development
are so high, and the costs of development so enormous, Government
needs to be careful not to further constrain useful drug development
with an increasingly stringent and rigid regulatory regime. An
example of such constraint is the requirement for primate research
for certain types of pre-clinical assessment. If the costs and
barriers for drug development continue to increase, fewer new
drugs will comes to market, thus stifling innovation and, more
importantly, potential patient benefit.
2.4 The increasingly high costs of drug
development also mean that pharmaceutical companies are less willing
to take risks in developing drugs. This is particularly the case
when developing drugs for small patient populations, such as some
cancers.
2.5 We welcome the European Commission call
that support is needed for further research on rare and orphan
disease[6]
areas, given their current neglect by the pharmaceutical industry[7].
The majority of clinical research in this area is funded by the
non-commercial sector. Cancer Research UK, for example, funds
clinical trials conducted by the United Kingdom Children's Cancer
Study Group. There is little incentive for industry to conduct
research aimed at small patient populations.
2.6 It is important that studies are carried
out which identify which subgroups will benefit from particular
therapies. There is currently a lack of pharmaceutical industry
funding for these studies, which will, in effect, reduce market
size for their products. However in the long term such studies
can reduce the drug costs for the NHS by only treating those that
will benefit. It is the responsibility of Government, possibly
through the academic sector, to ensure that such studies are carried
out, and the cost of the resulting diagnostic approaches is met.
3. QUESTION 2:
THE IMPACT
OF THE
PHARMACEUTICAL INDUSTRY
ON THE
CONDUCT OF
MEDICAL RESEARCH
3.1 Cancer Research UK undertakes certain
projects in collaboration with pharmaceutical companies. However,
there are many areas of our work in which pharmaceutical companies
do not have a strategic interest. Examples of these include the
development of drugs aimed at cancer in children and orphan conditions,
or radiotherapy and preventative research.
3.2 Currently there is no obligation on
pharmaceutical companies to publish the results of all trials.
Whilst studies have shown that pharmaceutical support does not
affect publication of late phase clinical trials[8],
studies comparing all clinical trials have indicated overall that
pharmaceutically sponsored trials are less likely to be published[9],[10].
This is of concern as a failure to publish can lead to overestimation
of treatment effects, which has the potential to lead to inappropriate
treatment decisions. We welcome recent decisions from some pharmaceutical
companies (most recently Eli Lilly and GlaxoSmithKline) to publish
all research results on the web, and would encourage other companies
to follow suit. Ideally these results would be best placed on
a comprehensive database for registration of all trials and their
results.
3.3 It is important that the pharmaceutical
industry is not only focused on specific endpoints in medical
trials, but investigates the wider effects of drugs. This information
would not only be useful in the drug development process, but
also to the wider clinical community when the drug comes to be
used in practice or in future research.
3.4 Increasingly research and development
conducted on behalf of the pharmaceutical industry is relocating
away from the UK to countries presenting larger markets for pharmaceutical
products. As long as the UK National Health Service lags behind
in adopting new treatments, the pharmaceutical industry will increasingly
look elsewhere for future research and development investment.
Research and development conducted for the pharmaceutical industry
underpins non-commercial medical research in the UK, and the loss
of such research activity would present a risk to UK medical research
capability as a whole.
4. QUESTION 3:
THE IMPACT
OF THE
PHARMACEUTICAL INDUSTRY
ON THE
PROVISION OF
DRUG INFORMATION
AND PROMOTION
4.1 The provision of accurate information
to patients, through our CancerHelp UK website and a team of information
nurses, is integral to Cancer Research UK's mission. On occasion,
Cancer Research UK does attend briefings on specific drugs by
pharmaceutical companies. However before any information is passed
on to patients, we take independent advice, and we will not promote
the prescribing of any one drug.
4.2 Cancer Research UK supports the current
regulations prohibiting direct-to-consumer advertising, and does
not believe that they should be relaxed.[11]
4.3 The increased emphasis on the development
of lobbying groups by pharmaceutical companies to raise interest
in the adoption of drugs or techniques is of concern. This can
result in groups or individuals pushing for action in a particular
area, without adequate consideration of the relevant evidence
base.
4.4 The funding of researchers by pharmaceutical
companies to publish papers in journals to promote particular
drugs in the absence of any new data should be discouraged.
5. QUESTION 4:
THE IMPACT
OF THE
PHARMACEUTICAL INDUSTRY
ON PROFESSIONAL
AND PATIENT
EDUCATION
5.1 Cancer Research UK provides information
on cancer prevention to General Practitioners and other health
care professionals.
5.2 Clinicians and researchers are offered
a great deal of unsolicited information and invitations from pharmaceutical
companies. It is therefore important, in the interests of transparency,
that there is a greater emphasis on declaration of interests for
all those involved in research, both in the not-for-profit and
pharmaceutical industries.
5.3 The European Medicines Agency reports
that patients are now actively looking for information on diseases
and medicines, and therefore providers of information should take
account of this trend.[12]
There is a need for clear, objective information for patients.
Whilst pharmaceutical companies offer information to patients
on treatments, this information will usually be linked to one
particular drug or service and may therefore not provide a full
picture of all the treatment options available. In this context
the work of NHS Information Partners service is welcomed.
6. QUESTION 5:
THE IMPACT
OF THE
PHARMACEUTICAL INDUSTRY
ON REGULATORY
REVIEW OF
DRUG SAFETY
AND EFFICACY
6.1 Cancer Research UK is not actively involved
in the regulatory review of drug safety and efficacy.
7. QUESTION 6:
THE IMPACT
OF THE
PHARMACEUTICAL INDUSTRY
ON PRODUCT
EVALUATION, INCLUDING
ASSESSMENTS OF
VALUE FOR
MONEY
7.1 Cancer Research UK responds to consultations
from NICE on the basis of the knowledge of experts in the field
and feeds their comments on draft guidance back to NICE on their
behalf.
7.2 Pharmaceutical companies have an important
role to play in providing information on drugs as they undergo
the process by which drugs achieve approval by the National Institute
of Clinical Excellence (NICE). During the appraisal of a given
drug, Cancer Research UK will therefore on occasion attend briefings
by manufacturers, as well as seeking independent advice.
7.3 The World Health Organisation (WHO)
review of the NICE Technology Appraisal Process referred specifically
to the influence the pharmaceutical companies have in this process.
The WHO recommended that NICE address the inconsistency that commercial-in-confidence
data will be accepted from pharmaceutical companies, whereas data
that are unpublished or in abstract form will not be accepted
from other sources.
7.4 In addition, the WHO recommended that
NICE should reduce duplication of effort in the assessment phase
of technology appraisal development as both manufacturers and
the appointed appraisal team produce separate reports to the NICE
Appraisal Committee for evaluation. The WHO recommended that the
appraisal team produce a single set of analyses incorporating
consultation with and input from the manufacturer. All analyses
carried out by the pharmaceutical industry should be subject to
careful scrutiny.
7.5 There is also some concern over the
influence that manufacturers have on the topics considered by
NICE for appraisal. Cancer Research UK has asked that more transparent
processes be put in place to define the process by which drugs
are referred for appraisal or not. We have also asked that a rationale
be provided for the process of prioritisation of drugs for appraisal
by NICE.
3 Registered charity no 1089464. Back
4
Newell DR, Searle KM, Westwood NB, Burtles SS. Professor Tom
Connors and the development of novel cancer therapies by the phase
I/II clinical trials committee of Cancer Research UK. British
Journal of Cancer. 2003;89:437-54. Back
5
Kola I, Landis J. Can the pharmaceutical industry reduce attrition
rates? Nature Reviews Drug Discovery, 2004;3:711-15. Back
6
An orphan disease is a disease for which no treatment has been
developed because of its rarity. Back
7
Commission of the European Communities. A stronger European-based
pharmaceutical industry for the benefit of the patient-a call
to action. 2003;35. Back
8
Krzyanowska MK, Pintilie M, Tannock Ian F Factors associated
with failure to publish large randomised trials presented at an
oncology meeting. Journal of the American Medical Association.
2003;290:495-501. Back
9
Dickersin K, Chan S, Chalmers TC, Sacks HS, Smith H Jr. Publication
bias and clinical trials. Control Clinical Trials. 1987; 8:343-353. Back
10
Easterbrook PJ, Berlin JA, Gopalan R, Matthew DR. Publication
bias in clinical research. Lancet. 1991;337:867-872. Back
11
Sullivan R. Direct-to-consumer advertising: the future in Europe.
Journal of the Royal Society of Medicine. 2000:93;400-401. Back
12
The European Agency for the Evaluation of Medicinal Products.
Discussion paper, the European Medicines Agency Road Map to 2010:
Preparing the Ground for the future. 2004;21. Back
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