Memorandum by AstraZeneca (PI 33)
TABLE OF
CONTENTS
| Summary |
1. | Introduction |
2. | Drug Innovation |
3. | The Conduct of Medical Research
|
4. | Provision of Drug Information and Promotion
|
5. | Professional and Patient Education
|
6. | Regulatory Review of Drug Safety and Efficacy
|
7. | Product Evaluation, including Assessments of Value for Money
|
SUMMARY OF
KEY POINTS
AstraZeneca is a responsible and ethical company
that works to improve the health and the quality of life of patients.
Great progress has been made in combating disease.
Technology developed over the past 15 years will further improve
our ability to continue to discover truly life-enhancing innovative
medicines.
Improvements in existing drug therapy by improving
tolerability and efficacy are equally important.
Discovering innovative medicines is expensive
and risky. It requires government to create a stable and competitive
environment that values science and innovation.
World-class medical research requires a renewed,
strong physical and procedural infrastructure in the UK.
AstraZeneca's commitment and investment in medical
research benefits the UK in many ways: economic, improved health,
improved medical research infrastructure.
All medical research is conducted according to
stringent international and national laws, regulations and guidelines.
AstraZeneca operates a 24 hour medical information
service about our medicines.
The provision of non promotional information would
support other high quality information services and counter misleading
information.
The ABPI self-regulatory code of marketing practice
provides wider control than statutory processes.
AstraZeneca has in place an effective approval
system for promotional material and activities and works hard
to ensure all aspects of its activity fully comply with the code.
Before any Sales Representative can have contact
with a health care professional he must have passed an examination
of the PMCPA and demonstrated thorough understanding of the medicine
he wishes to discuss.
AstraZeneca supports local education programmes
to assist in the implementation of National Service Frameworks.
AstraZeneca openly sponsors patient bodies in
order to improve access to good lay information and help patients
take greater responsibility for their health.
Interaction with Sales Representatives enables
healthcare professionals to gain access to the latest information
and ensures their continuing professional education.
Hosting clinical trials benefits the NHS by developing
the skills of the clinicians, enabling learning of key legislation
and protocol development.
The UK Government provides through the MHRA a
solid and objective regulatory system promoting the needs and
benefits of the British patients. This system further operates
within an effective and comprehensive European and international
framework that is constantly being updated and revised to reflect
new medicinal progress and scientific advances.
As a leading regulatory Agency in Europe it is,
however, very important that the MHRA fully supports and co-ordinates
their work with the European regulatory process, rather than duplicating
assessments being undertaken on behalf of Europe by European Committees
or the designated Reference Member State or Rapporteur Agency.
There is some evidence of such duplication and this is not in
the interest of an efficient regulatory process.
AstraZeneca works constructively with the HTA
bodies in England, Scotland and Wales in a transparent way and
in accordance with an agreed framework.
AstraZeneca contributes to both the appraisals
and clinical guideline programmes by submitting evidence and critically
reviewing drafts documents.
Further improvements in NICE process are, however,
still required. These include the addressing of NICE blight and
providing clarity about the relationship between health technology
appraisals and clinical guidelines including clarity on how the
decisions to review and update existing HTA guidance within the
context of a clinical guideline are made, and. In addition NICE
should work with respective bodies to address issues of implementation,
the consistency and quality of HTA groups and finally the duplication
of effort between NICE, SMC and AWMSG.
AstraZeneca welcomes the inquiry announced by the Health
Select Committee into the role of the pharmaceutical industry
and its influence on health policies, health outcomes and future
health priorities and needs and is pleased to submit written evidence.
1. INTRODUCTION
The industry and its influence
1.1 There are very few, if any, industries that are as
regulated as heavily as the pharmaceutical industry. Government
or their agencies regulate all activities of pharmaceutical companies
ranging from the discovery of a compound in the laboratory to
the authorisation to market a medicine.
1.2 Regulation is complex, time consuming and expensive.
It is not only right but also appropriate that companies like
AstraZeneca are able to discuss with government and their agencies
issues relating to their medicines. On average it takes about
12 years and £500 million to bring a medicine from the laboratory
to the patient. No other organisation will know more about the
medicine than the one that discovered it.
1.3 Ensuring patients' safety while at the same time
allowing rapid access to the most modern treatments is crucial.
1.4 Equally important, is balancing the needs of the
pharmaceutical industry for a stable business environment which
recognises and rewards innovation, with the requirement to provide
cost-effective medicines as one part of a sustainable and responsive
healthcare framework. Those governments that are successful in
finding the right balance are often equally successful in improving
standards of health (which in turn drives wealth creation) and
sponsoring a successful pharmaceutical industry.
History
1.5 AstraZeneca has a long and proud history of investing
in the United Kingdom and developing innovative medicines to treat
illness ranging from cancer and cardiovascular disease to infection.
1.6 Our discovery of medicines began during the war with
the development of Paludrine, an anti-malarial and Xylocaine,
a local anaesthetic. This tradition has carried on into the 21st
century. Most recently we have developed two groundbreaking treatments,
IRESSA for non-small cell lung cancer and EXANTA, an oral direct
thrombin inhibitor, the first alternative to warfarin in 50 years.
AstraZeneca and the United Kingdom
1.7 Within the United Kingdom, AstraZeneca has eight
principal sites and employs over 10,800 people. We have two Research
and Development centres of excellence in Alderley Park, Cheshire
and Loughborough, Leicestershire, two major manufacturing sites
in Macclesfield, Cheshire and Avlon near Bristol, UK sales, marketing
headquarters in Luton and corporate headquarters in London.
1.8 The United Kingdom represents just 3% of AstraZeneca's
total sales. Yet it remains an important location for its manufacturing,
research and development. Nearly a third of all its Research and
Development is conducted in the United Kingdom. Between 1999 and
2006 AstraZeneca's investment will approach £1 billion resulting
in over 550 new jobs. Nevertheless as a multi national company
with many sites across the globe competing for new investments,
the UK's sites must continually demonstrate their efficiency and
value for money.
Competitiveness of the industry
1.9 The government and its citizens need a successful
pharmaceutical industry in the United Kingdom. A successful pharmaceutical
industry benefits not only the economy in terms of the high quality
employment it offers and the positive contribution it makes to
the balance of payments, but also to the health of the nation.
A healthy nation correlates favourably with high economic performance.
1.10 Just as the National Health Service (NHS) needs
a strong and successful pharmaceutical industry to enable it to
treat and cure the millions of patients it sees every day so the
pharmaceutical industry needs the government to create a competitive
environment that encourages and rewards innovation in the United
Kingdom.
2. DRUG INNOVATION
Leading in Innovation
2.1 While healthy people may value innovation in terms
of a smaller, faster laptop, those who are sick only care about
getting well again. For these people, the pharmaceutical industry
has demonstrated its innovation in delivering a succession of
new medicines over the last 50 years, which have saved lives and
increased quality of life.
2.2 There have been many significant new medicines in
the last 50 years. Many of these improvements are the result of
completely new therapies; others are the results of incremental
advances with the latter often not as valued as much as it should
be.
2.3 The industry has in fact worked diligently on both
fronts. All involved in drug discovery want to deliver big breakthroughs
where possible, but they also recognise that the safety and efficacy
of existing drugs often needs improvement. In AstraZeneca, we
have been able to deliver on both radically new drugs and also
on valued improvements to existing drug classes. Our pipeline
is delivering a high proportion of drugs, which are being considered
as breakthroughs. About three-quarters of AstraZeneca's R&D
expenditure is targeted towards diseases identified by the UK
government as priority areas: cancer, coronary heart disease,
mental health, diabetes and diseases of the elderly.
Drug Discovery is Changing
2.4 It should be realised that, in discovering new drugs,
the industry is very dependent on the state of mankind's knowledge
of how the human body works and of what goes wrong in disease.
Drugs launched in the last few years today were discovered with
a much more limited science base than the ones that are being
discovered today and will be launched in the 2010s. Also the drugs
that dominate the market today reflect the drug hunting approaches
of the pastfor example mimicking the body's natural hormones,
exploiting the activity of natural products from plants and following
up side-effects noticed in clinic practice. This has inevitably
limited the industry's ability to find breakthrough drugs. It
has also limited the disease areas that were addressed, leaving
many diseases with little or no effective treatment.
2.5 Fortunately, things are set to improve. In the last
10-15 years there have been several significant improvements in
our ability to discover innovative new drugs. These are starting
to impact on new drug launches with the impact continuing to increase
over the coming 10-15 years.
2.6 Firstly, in the nineties, there were several improvements
to the way that the industry discovers drugs. For example, new
molecular biology techniques enabled us to work with purified
human protein targets, rather than with crude extracts of less
relevant animal proteins. High throughput screening emerged as
a significant way of finding compounds with drug activity. Our
ability to design drugs at a computer has improved with increased
computer power and new approaches to determining the 3D shape
of protein targets. In addition, a whole "drug discovery
technology" industry emerged, offering a huge range of new
techniques and approaches for making R&D more efficient and
effective. AstraZeneca has invested considerably in these new
approaches. For example, we have a leading position in protein
structure determination and have augmented our capability for
structure-based drug discovery with collaborations with a leading
British Biotech company in the field, Astex.
2.7 Secondly, in the last 10-15 years, there has been
an acceleration in our ability to understand disease mechanisms
at a molecular level. This has been fuelled by, for example:
Massive investment in the biological sciences,
particularly by the NIH in the USA.
The completion of the Human Genome Project.
Investment in the Biotech sector.
The emergence of powerful new tools such as microarrays,
protein mass spectrometry, imaging and bioinformatics.
A New Wave of Drug Discovery
2.8 The net effect of these investments is that many
diseases are now starting to be understood much better at the
molecular level. This includes some of the more difficult diseases
where society is looking for big improvements, eg cancer, Alzheimer's,
schizophrenia and the chronic inflammatory conditions such as
rheumatoid arthritis. With these new techniques and the ever-improved
understanding of disease, the industry is well placed to make
good progress against these and other diseases.
2.9 While the impact of these investments lies mainly
in the future, we are beginning to see the fruits today. For example,
in AstraZeneca, we have been able to build on the explosion of
knowledge of the molecular basis for cancer in the discovery of
our innovative cancer drug "IRESSA", described
as the biggest advance ever in the treatment of lung cancer. This
shows that investment in basic science together with innovative
drug hunting can lead to paradigm shifts in treatment. But, to
emphasise, it is a partnership: success that is still highly dependent
on the broad progress in biomedical science outside the industry.
Improving on Existing Drug Therapies
2.10 We should not underestimate the importance of improving
on existing drugs. For example, AstraZeneca's new anti-coagulant,
Exanta, is a huge improvement on the standard therapy, warfarin:
it is faster, much safer and does not require anticoagulation
monitoring. The significant health economic benefits will allow
the NHS to direct the funds saved elsewhere.
2.11 Furthermore, it has always been well known that
people differ considerably in their response to a given drug,
either due to their genetic make-up, or due to subtle differences
in the type of disease they have. This can lead to ineffective
prescribing and non-compliance by the patient. Our understanding
and ability to address this issue is improving fast. In AstraZeneca,
we have invested considerably in the new field of "pharmacogenetics",
with the aim that our medicines should be effective and safe for
all patients.
Enabling Innovation
2.12 In summary, the level of innovation in the pharmaceutical
industry has always been high, and is set to get even higher.
In the coming few decades, we should see the fruits of the science
and technology investments of the past. AstraZeneca's pipeline
is already showing this. But pharmaceutical R&D is inherently
risky, and tackling the diseases that are hard to cure is always
going to be more risky than those we know more about. The cost
of innovation is high and rising. The latest estimates put the
cost of developing each drug at £500 million. For this enterprise
to continue to deliver value for society well into the future
there is a need for governments to provide stability for the industryin
terms of recognising and rewarding innovation supply of talent,
funding biomedical science, maintaining IP rights, defending necessary
animal experimentation, and encouraging the Biotech sector. Governments
therefore have a key role to play in creating the climate in which
innovation can thrive and deliver value to society.
3. THE CONDUCT
OF MEDICAL
RESEARCH
The Value of Medical Research in the United Kingdom
3.1 There is no doubt that new medicines can bring about
significant improvements in patient health. High quality medical
research is essential for the discovery and development of such
life enhancing new medicines and medicines that will deliver improved
patient health. AstraZeneca invests heavily in medical research
for these reasons and needs a commercial return on its investments.
The United Kingdom has, to date, provided an excellent environment
in which to conduct medical research, and AstraZeneca has a significant
commitment to Medical Research the UK. Even though the UK represents
only 3% of our total market, more than 10% of the patients involved
in our clinical trials live in the UK. At our R & D sites
in Alderley Park, Cheshire and Loughborough, Leicestershire and
in our marketing company, in Luton we have over 1,000 people devoted
to the design, conduct, analysis and interpretation of medical
research. Each year we work with more than seven hundred clinical
investigational centres in the UK conducting more than one hundred
clinical studiesmany of them multinational collaborations.
Our track record of important medical research in the UK is second
to none and has resulted in many key medicines, such as treatments
for cancer (Nolvadex, Zoladex, Casodex, Arimidex and Faslodex),
cardiovascular disease (Inderal, Tenormin, Zestril, CRESTOR),
anaesthesia (Diprivan) and psychiatry (Seroquel). Most recently,
medical research in the UK led to the discovery of IRESSAthe
first of a new generation of well tolerated medicines for lung
cancer now licensed in many countries including the US but not
yet licensed in the UK.
The Conduct of Medical Research
3.2 Patient care is of paramount importance to AstraZeneca.
We fully support the regulation and stringent control of medical
research.[3] We conduct
all our medical research according to international and national
laws, regulations and guidelines as established by UK Government,
and other bodies such as the European Medicines Agency and the
US FDA. We welcome opportunities for positive interactions to
develop regulations and guidelines whilst recognising the need
for complete independence of the regulatory bodies; for example,
AstraZeneca has contributed to defining best practice in the ethical
conduct of pharmacogenetics studies and we have collaborated with
the Department of Health (DoH) to develop a model clinical trials
agreement.
3.3 All AstraZeneca and investigational site staff involved
in the conduct of our clinical trials receive extensive training
in Good Clinical Practice (GCP); this training better equips the
site for future work, whether industry sponsored or academic.
3.4 AstraZeneca is committed to providing healthcare
professionals and patients with relevant information that enables
them to make the best treatment decisions. AstraZeneca has put
in place a mandatory Publication Policy that outlines the company's
principles with regard to external communication of scientific
and medical information. Specifically this policy describes the
company's aim to publish the results of AstraZeneca-sponsored
clinical trials; our commitment to maintain high standards of
medical and scientific integrity by presenting research results
in an accurate, objective, and balanced fashion; and states that
selective publication that would misrepresent the medical profile
of an AstraZeneca product is not acceptable. Compliance with this
policy is formally monitored.
3.5 Our ethical principles are publicly documented and
rigorously implemented.[4]
Wider Benefits of AstraZeneca's Contributions to Medical Research
in the UK
3.6 In addition to directly benefiting patients, we believe
that our contributions to Medical Research in the UK bring wider
benefits by raising the overall quality of medical research science
in this country not only in terms of the science of therapeutics
but also the development and application of novel technologies
(particularly genomics, proteomics and imaging). Via direct collaboration
or by providing grants we support a significant number of non-drug
related medical research efforts. Collaborations include efforts
to understand better the pathophysiology of various diseases and
the development "biomarkers" to aid selection of dose
and to better target therapies to patients (the right drug at
the right dose for the right patient). We are also sponsoring
medical science aimed at reducing the frequency and severity of
drug induced side-effects, improving statistical analysis techniques
and speeding the collection and evaluation of clinical data from
patientsparticularly side-effect data.
The Future
3.7 AstraZeneca looks forward to further successful Medical
Research in the UK. We welcome the science and innovation investment
framework 2004-14,[5] however,
we do believe that the UK needs a renewed and deepened pool of
talented medical researchers. The health service priority of service
provision has resulted in fewer people with time available for
medical research, and postgraduate medical training has placed
less emphasis on developing relevant skills (Strengthening Clinical
Research, Academy of Medical Sciences Report, October 2003).
3.8 AstraZeneca has, with other pharmaceuticals companies,
provided training fellowships in clinical pharmacology; we have
also independently sponsored clinical training fellowships, studentships
and courses. However, the training provision for physicians and
non-physician medical researchers in the UK remains inadequate
to provide sufficient individuals who are able to collaborate
with the industry either by direct participation in clinical studies
or by review, understanding and practical implementation of the
results of research.
3.9 Similarly, the UK needs to develop a strong physical
and procedural infrastructure to deliver world-class medical research.
The recent Pharmaceutical Industry Competitiveness Task Force
(PICTF) ReportPerformance Indicators (2003) notes the gap
between US and UK government expenditure in medical and biological
sciences expressed as a proportion of GDP. AstraZeneca has seen
the benefits of the development of the National Cancer Research
Network and NTRAC initiatives and has established clinical and
translational collaborations with these organisations. AstraZeneca
strongly supports the recent initiatives to establish the UK Clinical
Research Collaboration and the NHS research networks for Alzheimer's
disease, Stroke, Diabetes, Mental Health and Children's medicines.
These initiatives should serve as a foundation for a renewed,
positive medical research environment but will require significant
financial investment beyond that already announced and eventual
extension into other important disease areas.
4. PROVISION OF
DRUG INFORMATION
AND PROMOTION
Importance of Information and promotional activities
4.1 The appropriate and safe use of medicines depends
on information about the medicine provided to health professionals,
patients and carers. A medicine used inappropriately is potentially
dangerous and a medicine not taken at all is a waste of taxpayers
money. Pharmaceutical companies, such as AstraZeneca, are able
to provide very high quality information about medicines and on
health topics in general. Unlike many other providers of information
our communications are tightly controlled by effective regulation
and self-regulatory codes and by the company's commitment to quality.
4.2 A high proportion of prescribed medicines are not
taken as intended by the prescriber. Updated regulatory interpretations
could help companies to provide more, quality controlled, non-promotional
medicines information to patients and carers. AstraZeneca already
plays a valuable role in medicines and health information provision
and we believe this has a positive influence on health and wellbeing.
However, the full potential to maximise patient benefits has not
yet been realised.
Provision of Drug Information
4.3 Pharmaceutical companies can contribute to the safe
and effective use of their medicines through high quality Drug
Information Services and through Patient Information Leaflets
(PILs) in packs. However, current interpretation of the regulations
prevents further provision of non-promotional information to patients,
which could lead to more informed decisions about treatment choices
being made.
4.4 AstraZeneca operates a 24-hour medical information
service to respond to queries about our medicines. Around 16,000
enquiries are answered annually in the UK using the company's
extensive information resources and expertisewe know more
about our medicines than anyone else. Most enquiries are from
health professionals. Health professionals are able to seek medicines
information from password-controlled company Internet sites.
4.5 However, the majority of enquiries about their medicines
that comes directly from patients and their carers cannot be fully
answered because this would be construed as an illegal promotion
of a prescription only medicine to the public. At present patients
can find out more information about the safe use of tamoxifen
(to treat breast cancer) from the Internet than they can from
the company who discovered it, despite the fact that most of the
information available on the Internet is unauthorised and, sometimes,
misleading. The provision by companies of non-promotional information
to patients about the medicine they have been prescribed would
support other high quality information sources such as NHS Direct.
It would contribute significantly to the optimum and safe use
of medicines.
4.6 The PIL that is provided in packs is constructed
to a design set out by an EU directive with little flexibility
to enhance its user-friendliness. AstraZeneca fully supports the
recent EU developments with respect to the requirement for user
testing of leaflets. We are also actively supporting the CSM working
group on patient information that aims to recommend improvements
in PILs.
4.7 PILs are continually updated during the life of a
product. Up to date texts are provided on the Internet in response
to any change. However, since companies are prohibited from including
the website address on the leaflet, patients have no way of knowing
that there may be more up to date information available to them.
Promotional Activities
4.8 Promotional activities to healthcare professionals
are closely regulated and AstraZeneca is committed to promoting
our medicines responsibly and ethically (See point 5.2 for additional
information).
4.9 The ABPI self-regulatory code of marketing practice
provides wider controls than statutory processes. It is regularly
updated to reflect the current consensus on acceptability, external
developments (eg the Internet) and to reflect current best practice.
The UK system for ensuring the quality of promotional communications
is amongst the most effective in the world with regulation (through
MHRA) working alongside self-regulation (ABPI code).
4.10 The ABPI Code covers industry activities where questions
could be raised about the level of influence; clear guidelines
exist for sponsorship and hospitality arrangements and the provision
of promotional aids (low value gifts). This evolves over time
and is regularly updated taking full account of the views of professional
bodies, regulators, pharmaceutical companies (including AstraZeneca)
and other interested parties. For example, promotional reminder
gifts (pens, pads etc) carrying a product name are permitted up
to the value of £6 providing they are relevant to professional
practice. In future the consensus view on the appropriateness
of such gifts might change, based on complaints and subsequent
judgements based on the existing code. If it does the mechanism
is established whereby changes can be rapidly implemented.
4.11 AstraZeneca has in place a rigorous approval system
for promotional material and activities. The requirements for
this approval process of materials and activities are set out
in a regularly reviewed standard operating procedure. One such
requirement is that no promotional material or activity can proceed
without the signed authorisation of two Prescription of Medicines
Code of Practice Authority (PMCPA) and (MHRA) registered company
signatories, one of whom must be a medical practitioner. Furthermore,
any complaints that are received and upheld are thoroughly investigated
and remedial actions put in place to prevent recurrence. The Medical
Director must sign a written undertaking that there will be no
recurrence of the matter. Our representatives receive training
and regular updating on the technical aspects of our products
and also on ethical marketing and selling practices. Failure of
sales and marketing personnel to comply with high standards is
taken very seriously and is a disciplinary offence. Globally AstraZeneca
company policies and standards and our corporate responsibility
policy cover sales and marketing.[6]
4.12 AstraZeneca does not advocate any change in the
law which would permit Direct to Consumer advertising of prescription
medicines, including the type of TV and press advertisements seen
in the USA. These are not permitted in the EU and this position
has recently been reconfirmed in the review of pharmaceutical
legislation. Pharmaceutical companies, however, do have a role
to play alongside other information providers, in the provision
of non-promotional information about medicines and diseases, directly
and indirectly to patients and the public. AstraZeneca supports
the development of clear quality guidelines for all providers
of non-promotional medicines information. The information provider
should always be identified, but the acceptability of a piece
of information should be based on its quality, reliability and
usefulness rather than its source.
4.13 AstraZeneca believes that companies be encouraged
to work with MHRA to find ways whereby their knowledge of medicines
and their communication skills are allowed to be used to maximum
effect to the benefit of patients.
5. PROFESSIONAL AND
PATIENT EDUCATION
5.1 AstraZeneca works hard to ensure that in all activities
involving both Health Care Professionals (HCPs) and patients about
its products, UK legislation and the requirements of the PMCPA
are fully complied with.
Ensuring Appropriate Use of Our Medicines
5.2 HCPs are kept fully updated on the advances in drug
therapy through interaction with AstraZeneca's sales representatives.
Representatives educate HCPs on the correct use of the Company's
medicines through reference to data and licensed indications.
Before contact with an HCP, all sales representatives must have
both a thorough understanding about the medicines they wish to
discuss, and have passed an official examination set by the PMCPA
on the regulations concerning the interactions they may have with
health professionals. The PMCPA sets strict guidelines regulating
how sales representatives may interact with HCPs.
5.3 When there are changes to the licences of AstraZeneca's
medicines, its Medical Information Department sends out written
notifications to all relevant parties. Occasionally, if there
is a change in a licence that should influence prescribing such
as a safety concern, AstraZeneca will use the "Dr Doctor"
letter format to communicate those changes.
5.4 Our Medical and Market Access and Outcomes Research
Departments provide unbiased information on our products to assist
formulary applications and decisions, including the provision
of health economic/cost-effectiveness data/models.
5.5 AstraZeneca provides supplementary patient and physician
educational materials to support the Summary of Product Characteristics
and PILs Last year AstraZeneca participated in the in the Medicines
Guides programme which, in conjunction with NHS Online, provides
factual information about diseases and the treatments available.
5.6 In partnership with the MHRA and the NHS, AstraZeneca
develops Patient Risk Management programmes, which are designed
to support the safe use of our medicines.
5.7 AstraZeneca has supported local educational programmes
assisting the uniform implementation of National Service Frameworks
(NSFs). Advice from bodies providing National Guidance has also
been incorporated into company presentations to local Drug and
Therapeutic Committees (DTCs), to help in the implementation of
such guidance.
Patient and Disease Awareness
5.8 To support initiatives from Government and encourage
patients to take a greater responsibility for their health, it
is vital that patients to have easy access to good quality lay
publications on disease areas to inform them in their discussions
with their prescriber. AstraZeneca sponsors disease area websites
and other patient educational materials, which are fully compliant
with legislation and the ABPI Code of Practice. In one instance
a grant was awarded to support an Internet based patient self-management
programme run by the Manic-Depression Foundation. This programme
has facilitated a wider dissemination of knowledge concerning
mania and depression to both patients and carers, and provided
a forum for discussion around this important disease.
Patient Group Support
5.9 AstraZeneca is an acknowledged sponsor of a wide
spectrum of patient bodies / associations such as the Prostate
Cancer Coalition, and the British Heart Foundation. We share information
on our medicines with these groups and support the production
of patient educational activities and material. The Prostate Cancer
Coalition Roadshow programme in 2003 was a good example of such
sponsorship.
Continuing Educational Opportunities for Health Care Professionals
5.10 Treatments for diseases are constantly changing.
With the increasing demands upon HCPs they have neither the time
nor the resource to adequately update themselves on advances in
those treatments, which will ensure the optimum benefit for their
patients. This is especially the case in those areas not directly
linked to the HCPs own practice. Interaction with AstraZeneca's
Medical and Sales personnel and AstraZeneca sponsored local, regional
and national meetings enables prescribers to gain access to the
information as well as ensuring their continuing professional
education. AstraZeneca also supports attendance at key conferences,
and post-conference educational meetings. This provides a forum
for Key Opinion Leaders to share with colleagues and peers important
data emerging from major congresses, such as the American Society
for Clinical Oncology (ASCO)
5.11 AstraZeneca has and does sponsor NHS bodies and
patient groups to help them develop educational programmes to
assist in the roll-out National Guidelines such as those produced
by the National Institute for Clinical Excellence (NICE). One
such example are those guidelines directed to NHS Mental Health
Trusts, where the Company has worked with the National Institute
for Mental Health in England (NIMHE) to develop and support the
NICE Guideline on schizophrenia at their national conference.
Professional Development
5.12 AstraZeneca supports the further professional development
of NHS staff by the sponsorship of tailored educational and training
programmes that have been approved by professional colleges /
bodies. Asthma nurses working in General Practice have for example
received sponsorship to gain the Diploma in their chosen speciality,
benefiting both as individuals and their patients.
5.13 The UK pharmaceutical industry widens career opportunities
for HCPsDoctors, nurses, pharmacistswho want to
gain exposure to business and research environments. AstraZeneca
offers secondments for clinicians in special units, eg rotations
between Trusts in the North West and our Clinical Pharmacology
Unit. In addition those HCPs who enter the industry either on
a temporary or permanent basis use the research and business skills
for the benefit of the NHS units/staff they have contact with
often acting as mentors and coaches in management.
Clinical Trials
5.14 The pharmaceutical industry offers expertise in
clinical trial design and implementation which raises the standards
of clinical trials in the wider NHS, through training on key legislation
and policies in clinical trial practice, eg Good Clinical Practice,
EU Clinical Trials Directive, protocol development, and ethics
submission.
5.15 The Company supports numerous research ideas from
UK clinicians, allowing the development of research skills in
the NHS, and supporting continuing advancement in clinical and
scientific medicine. In psychological medicine, the UK focuses
on supporting research ideas on a number of key centres such as
the world-renowned Institute of Psychiatry in London. Here a number
of studies by leading clinicians have been supported by AstraZeneca,
many of which have been turned down by Government bodies due to
a lack of available funds.
5.16 AstraZeneca commits to the policy that the results
of all AstraZeneca sponsored clinical studies whether perceived
as positive or not to the Company should be made available to
the wider community.
6. REGULATORY REVIEW
OF DRUG
SAFETY AND
EFFICACY
6.1 In almost all countries in the world, concerns have
been expressed over public health and product safety in a number
of areaspharmaceuticals being only one of them. With respect
to medicines, governments have responded by placing requirements
on manufacturers to obtain marketing authorisations before placing
medicines on the market and to conform to stringent on-going testing
procedures. All aspects of activities in these areas are regulated
and legally tightly controlled. The pharmaceutical industry is
arguably the most highly regulated industry in the UK, and operates
within a very effective and comprehensive European and international
regulatory framework that is constantly being updated and revised
to reflect new medical progress and scientific advances. The amount
of pharmaceutical regulation has increased significantly over
the past couple of decades and there has been greater international
exchange of medicines information between national regulatory
authorities, aimed towards increasing the protection of patients.
6.2 The pharmaceutical industry, medical community, patients
and government all have a common interest in ensuring that the
regulatory system in the UK is transparent, efficient, robust
and bases its decisions on a high standard of scientific evidence.
Government has a particular important role to play here in ensuring
that new regulation is well formulated, targeted and meaningful
ie actually responds to a real need. The regulatory system should
provide timely access for patients to effective medicines, whilst
ensuring patient safety, and stimulating research into new treatments.
Marketing Authorisation Application
6.3 Before a company can market a medicine in the UK,
expert committees within the MHRA or the EMEA[7]
must assess whether or not the medicine should be authorised.
Before a marketing authorisation is issued, the Agencies will
carry out close scrutiny of all the technical reports that must
be generated during the development of the medicine, and review
the proposed manufacturing methods, quality control procedures
and evidence of pharmacological activity, clinical safety and
efficacy. The average regulatory submission for a new medicine
consists of several hundred volumes of technical and scientific
reports and data. During this activity, the "assessment",
the Agency assessors will critically review all the scientific
evidence presented by the applicant company to establish that
the medicine's quality, safety and efficacy are fully supported
by the data and in accordance with current rules and regulations.
Of necessity, these rules and regulations are based upon a complex
combination of law, science and medicine and call for specialised
training and background to interpret correctly. The regulatory
environment is also often subject to rapid change in accordance
with the development of scientific methods and new technologies
to which the regulatory requirements need to adapt.
Role of Independent Experts in the Provision of Advice to MHRA
6.4 The MHRA is assisted by advisory committees in making
licensing decisions and in reviewing the safety of marketed medicines.
It is in the interest of all stakeholders to make sure that the
highest level of medical and scientific expertise and excellence
is available to the MHRA through these committees. There is, however,
only a limited pool of experts in any given area at any given
time, and it is important to recognise that this national resource
of independent expertise needs to be accessible to both industry,
and the MHRA. Consequently, it is essential to have in place a
robust, transparent and effective system to avoid any potential
conflicts of interest for experts in relation to a specific medicinal
product. The MHRA operates just such a system, whereby committee
members are subjected to a high level of transparency and rigorous
declaration of personal interest, to ensure that their expert
scientific opinion is independent and unbiased.
6.5 Industry representation on some advisory committees
is valuable to provide input to the discussion of the practical
consequences of health policy decisions and on the implementation
of these decisions such as switching from BANs to INNs, nurse
prescribing and improving the quality of patient leaflets based
on experience of drug development and manufacture.
Financial Structure of the MHRA
6.6 The Evans-Cunliffe report[8]
recommended that the full cost of the then Medicines Directorate
should be charged to the pharmaceutical industry. Therefore, the
Agency was established as a Trading Fund that had to be self-sufficient
and recoup its costs through fees charged to the industry for
its assessment and control activities.
6.7 AstraZeneca is supportive of the MHRA being properly
funded so that it can operate efficiently and effectively as a
centre of regulatory excellence in Europe. There are sufficient
checks and balances in place to ensure independence from industry.
Fee levels are set by the Treasury, following public consultation,
and are detailed in the relevant UK statutory instruments.[9]
However, the pharmaceutical industry has asked for greater transparency
from the MHRA on how income from fees are allocated, particularly
since the merger of the Medicines Control Agency (MCA) and Medical
Devices Agency (MDA) as most of MDA's activities were funded by
the Government, to ensure that the fees for control of medicines
are not subsidising activities related to medical devices.
Post Marketing Authorisation Phase
6.8 If a medicine is approved and obtains a licence to
be marketed this does not mean that the assessment of the medicine
is finished but instead marks the beginning for the applicant
company of a legal obligation continuing throughout the lifetime
of the medicine to provide the MHRA with information about the
medicine both at regular intervals and on an ad hoc basis. The
benefit/risk assessment of a medicinal product is a continuous
process.
6.9 At the time of approval there will be extensive clinical
data on the use of the medicine, however, companies have global
pharmacovigilance/risk management systems in place to monitor
and assess the use of the medicine in the wider population during
the marketing phase. Newly approved medicines and significant
changes to existing medicines are subject to intensive monitoring
by the MHRA as part of the Committee on the Safety of Medicines
(CSM) Yellow Card/Black Triangle scheme. This scheme allows rapid
monitoring of new safety signals as medicines become more widely
used in patients.
6.10 Additionally, pharmaceutical companies and the MHRA
are continuously monitoring the use of the medicines through review
of Adverse Drug Reaction (ADR) reports, which can arise from any
country where the medicine is marketed globally, and which companies
submit expeditiously to the MHRA. Companies also summarise these
reports regularly in Periodic Safety Update Reports (PSURs), which
are submitted to the MHRA for an in depth review. Changes to the
approved product information or labelling have to be based on
evaluated scientific evidence that involves open interaction between
the relevant parties. The aim of this is to ensure that the medicines
are used as safely as possible, without the risk of premature
removal from the market or unnecessarily restricting access to
patients who could benefit from the medicine.
6.11 The MHRA as well as companies regularly update the
product information and labelling so that healthcare professionals
and patients have access to relevant information on the safe use
of their medicines. As in most areas where regulatory requirements
are imposed, stringent restrictions are also placed on the claims
that can be made for the medicine in the labelling or in advertising.
6.12 The requirement for pharmacovigilance is embodied
in the pharmaceutical legislation and there are severe penalties
for non-compliance. MHRA also conduct regular inspections and
have enforcement powers if serious non-compliance is found.
Communication between Industry and Regulatory Authorities throughout
the Lifecycle of a Medicine
6.13 A high quality scientific assessment is facilitated
by objective scientific dialogue between regulatory authorities
and companies. Such regular dialogue is in the public health interest,
to ensure that effective and safe new medicines reach the patient
as quickly as possible. It is essential that this integral part
of the regulatory framework is continued throughout the various
regulatory processes, including pharmacovigilance. Good communication
channels between the MHRA and the company are also essential when
the MHRA requires information from the company, often at very
short notice eg paediatric data, TSE,[10]
safety reviews on particular classes of medicines.
6.14 There are clearly defined legislative requirements,
which necessitate communication, dialogue and the submission of
data from industry to the MHRA during the life-cycle of a medicine
eg expedited and periodic safety reporting. Regular scientific
discussion is initially needed between the pharmaceutical company
and the MHRA during the development of a new medicine. It takes
an average of 12 years to develop a new medicine and various issues
of a technical or scientific nature might arise during this process
where written guidance is not available. It is important to ensure
that the right development program is carried out to enable registration
of safe and effective new medicines in the most efficient way
and avoid unnecessary clinical trials or delays in getting new
medicines to the patients.
6.15 Therefore, during the regulatory review of a new
medicine, or a change to an existing medicine, there is an on-going
dialogue between the applicant company and the MHRA. The applicant
company explains the data, provides clarifications and answers
questions based on the scientific evidence provided. Through such
dialogue, the MHRA is able to make decisions on the safety, quality
and efficacy of the medicine based on the totality of the evidence
available and the proposed usage. For marketed medicines, companies
and the MHRA need to maintain regular dialogue to ensure the medicine
is used safely and effectively and the licence is kept in compliance
with all the relevant regulations. Such dialogue takes place between
companies and all major regulatory agencies worldwide.
6.16 A more specific example of where it is important
that industry and the MHRA work together is the optimal provision
of clear and effective information to patients about their medicines.
This is occurring currently with industry representation on the
CSM expert working group reviewing the quality of patient information
leaflets.
6.17 Input from the Industry and other stakeholders during
the drafting of guidelines is critical to highlight the practical
implications of guidance in relation to current and future development
standards, in addition to the ability to provide comments during
the formal consultation stage. The ICH[11]
process is founded on the basis whereby authorities and the industry
from the US, Japan and EU work together to generate and harmonise
regulatory guidelines that will be used in the three regions.
Areas for improvement
6.18 Not only is a strong, efficient and effective UK
regulatory agency necessary for ensuring the safety of public
health, it is also fundamental to drive a competitive locally
based pharmaceutical industry that can develop medicines to better
meet the needs of patients. The impact of the establishment of
the EMEA on the European regulatory environment has been significant.
Companies now have the possibility to select any one of the 25
Member States to assess their medicines. Experience shows that
companies select European regulatory agencies that not only provide
high scientific excellence, but also consider customer service
and performance.
6.19 The MHRA is considered to be one of the 4 or 5 leading
regulatory agencies in Europe. The MHRA has to ensure that it
takes a leadership role in developing the future network of regulatory
agencies, and dedicates sufficient resource and support to the
European system. Findings in the National Audit Office (NAO) Report
on the MCA[12] indicated
that the Agency would be looking to improve the quality of the
services it provides to industry in order to attract more business.
6.20 AstraZeneca recommends that the Health Committee
supports the ongoing development of the MHRA as the leading regulatory
agency in Europe, assuming that this is the Government's intention
for the future role of the MHRA.
6.21 Greater transparency is being called for from regulatory
procedures. The industry supports a robust and transparent regulatory
procedure, but recommends that the Health Committee does not only
consider transparency towards the public. Increased transparency
for companies during the assessment process allows better understanding
between the company and the MHRA of any issues, and results in
more efficient processes for dealing with them. It also ensures
that patients are provided with high quality, safe and effective
medicines to combat diseases that would otherwise remain untreated.
7. PRODUCT EVALUATION,
INCLUDING ASSESSMENTS
OF VALUE
FOR MONEY
7.1 AstraZeneca are committed to working with all Health
Technology Assessment (HTA) bodies (NICE, SMC and AWMSG) to ensure
equitable access to medicines. We are actively engaging with each
of these bodies through a range of activities including submission
of evidence, responding to consultations on matters of process
and membership on a number of committees. In addition to providing
information and technical expertise we are, via our work and interactions
with each of the HTA bodies, able to share our experiences of
best practice. Each of these activities are vital towards ensuring
that clear and credible guidance is issued benefiting both patients
and the NHS and ensuring equitable access to medicines.
National Institute for Clinical Excellence (NICE)
7.2 Since the conception of the NICE in 1999, AstraZeneca
have played a key role in submitting data for both the appraisals
and guideline programmes, participating in the consultations on
NICE processes and representing industry on both the appraisals
and guideline committees.
Health Technology Appraisals
7.3 To date, AstraZeneca have submitted evidence for
five health technology appraisals and we are currently involved
in preparing four further submissions.
7.4 AstraZeneca are committed to providing information
to NICE in a transparent manner in accordance with the agreed
framework on the use of confidential data. Industry submissions,
such as those provided by AstraZeneca enhance the information
available to the HTA groups. In addition to providing information
on clinical data industry submissions include detailed information
on cost-effectiveness including the provision of QALY values and
in-depth health economic modelling. Information on NHS resource
implications is also provided. In the case of new medicines, which
are due to be appraised near to launch industry submissions may
be the primary source of detailed information available to the
HTA groups. NICE have themselves recognised the value of industry
submissions in the appraisals process and did not adopt the WHO's
recommendations that the Appraisals Committee should be presented
with a single set of analyses.[13]
7.5 In addition to submitting data AstraZeneca also critically
reviews and comments on all appraisal documentation released for
consultation with the view to ensuring the final guidance is clear,
credible and robust.
Guidelines
7.6 AstraZeneca also actively contributes to the clinical
guideline programme by both submitting evidence and critically
reviewing drafts for a wide range of guidelines. In submitting
evidence, in addition to providing details of current data, we
also provide information on data/publications that will become
available within the development time of a guidelineBy
doing so, the National Collaborating Centres can develop a final
guideline which takes into account all the data which will be
available at the time the guideline is published.
7.7 AstraZeneca are, however, concerned about the lack
of appeal within the clinical guideline process. While stakeholders,
including industry, are able to comment on the draft guidelines
there is no course of action, which can be taken to challenge
the final guideline.
Representation on NICE committees
7.8 NICE welcomes the contribution of pharmaceutical
industry consultees on a number of their committees. Currently
AstraZeneca represent the industry on a Clinical Guideline Review
Group and have previously represented the industry on one of the
Appraisals Committees.
7.9 It is our view that such industry representation
enhances the depth and quality of the committee discussions.
Processes/procedures
7.10 AstraZeneca play an active role in developing and
improving NICE procedures and processes, via both participation
in consultations and also via membership of the ABPI's National
Health Technology Assessment/Clinical Guidelines (NHTA/CG) User
Group. Our aim is to work with NICE to ensure that the NICE processes
are efficient, fair and transparent and result in robust and sustainable
guidance.
7.11 In working towards improvement AstraZeneca have
participated in all NICE process consultations since 1999, including
the recent appraisals Process and Methods consultation. We are
currently responding on the recently announced consultation for
interim appraisals.
Implementation of NICE guidance
7.12 We look forward to collaboration with NICE on the
issue of implementation. In the review of implementation to date,
AstraZeneca have provided information to inform the report produced
by Professor Mike Richards.
All Wales Medicines Strategy Group (AWMSG) and Scottish Medicines
Consortium (SMC)
7.13 AstraZeneca works closely with both of these groups
via membership on the relevant ABPI User Groups and, in the case
of the SMC, participation in appraisals. As Scotland and Wales
are outside of the remit of the Health Select Committee we will
not discuss our collaboration with these groups in detail but
would be happy to discuss at a later date if required.
Areas for improvement
7.14 While improvements to NICE processes have been progressed
since the Health Select Committee review there remains area where
further improvements could be made. In focusing on these AstraZeneca
suggest the following recommendations:
7.15 The Department of Health in conjunction with NICE,
the Healthcare Commission, the NHS and industry continue to focus
on implementation taking into account the recommendations of Professor
Richard's report.
7.16 NICE continue to address and avoid the potential
issue of "NICE blight" in those instances where guidance
will not be available at launch. We recognise the step taken by
NICE to address this by working with the National Prescribing
Centre on the production of drug monographs, however, we would
recommend that NICE both work to actively direct the NHS to these
monographs and monitor the effectiveness of these in reducing
NICE blight.
7.17 NICE to provide clarity about the relationship between
technology appraisals and clinical guidelines and the criteria
used to define how technologies are assigned to each. We would
particularly welcome further clarity and transparency on how the
decisions to review and update existing HTA guidance within the
context of a clinical guideline are made.
7.18 The DoH and the National Coordinating Centre for
Health Technology Assessments review each HTA group for quality
and consistency and ensure each has the necessary resource capability.
7.19 The Department of Health, Welsh Assembly Government
and Health Department of the Scottish Executive review the processes
of the three separate technology appraisal systems and, in order
to avoid the current duplication of effort that currently exists
both for the three HTA groups and stakeholders, devise a mechanism
for sharing best practice.
3
EU Clinical Trials Directive 2001/20/EC, Good Clinical Practice,
GCP; http://www.mca.gov.uk/. Back
4
http://www.astrazeneca.com/Article/11115.aspx. Back
5
www.hm-treasury.gov.uk. Back
6
http://www.astrazeneca.com/article/11123.aspx. Back
7
European Medicines Agency approves medicines for the European
market ie all 25 countries including the UK. Back
8
Evans N J B, Cunliffe P W. Study of Control of Medicines, December
1987. Back
9
Medicines for Human Use (Marketing Authorisations, etc) Regulations
1994. Back
10
Review of all medicines to minimise the risk of transmission
of Transmissible Spongiform Encephalopathies. Back
11
International Conference on Harmonisation of Technical Requirements
for Registration of Pharmaceuticals for Human Use. Information
available from: www.ich.org. Back
12
Safety, quality, efficacy: regulating medicines, report by the
Comptroller and Auditor General, HC 255 Session 2002-03, 16 January
2003, p 14-15. Back
13
Hill S et al. Technology appraisal programme for the National
Institute for Clinical Excellence: Second report of session 2001-02.
London: The Stationary Office Limited; 2002. Back
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