Memorandum by GlaxoSmithKline (PI 51)
EXECUTIVE SUMMARY
GlaxoSmithKline (GSK), along with the rest of
the pharmaceutical industry, makes a very strong contribution
to the health and wealth of the UK. The company does this in a
number of ways:
— GSK has its headquarters in the UK
where it employs over 21,000 people.
— GSK believes that the UK has to remain
competitive in the global marketplace in order to attract and
retain investment by the pharmaceutical industry.
— GSK invests around £2.8 billion
in research and development (R&D) each year with over £1
billion directly in the UK. GSK is the largest investor in R&D
in the UK. At the cost of almost £4 million, GSK is supporting
375 PhD. studentships—more than any other company in the
UK.
— GSK's total expenditure on global
community programmes is the largest of any UK company. In 2003,
such expenditure amounted to £338 million and £11 million
in the UK.
— GSK has pioneered significant innovation
in medicines development with many "first in class"
therapies that have revolutionised patient care in diseases such
as asthma, diabetes and HIV/AIDS.
— Animal extremism is one of the biggest
problems facing the research-based industry. The Government needs
to act to control this threat through legislative action and effective
enforcement.
— GSK provides high quality medical
information to support health care professionals. The company
handled over 30,000 telephone calls in 2003 both in and out of
office hours.
— In providing information to health
professionals, patients and the public, GSK strives to meet the
highest ethical standards and adheres to the ABPI Code of Practice
and all other relevant professional codes.
— GSK actively supports the personal
development of health care professionals, assisting health care
professionals to achieve major objectives in their educational
plans.
— In June 2004 the company announced
the creation of the GSK Clinical Trial Register, an electronic
database to enable dissemination over the Internet of information
about GSK-sponsored clinical trials.
— The pharmaceutical industry operates
within one of the most complex and regulated frameworks of any
industry. Good communication and high quality scientific assessment
between regulators and companies is essential to ensure the regulatory
system is efficient and effective, ensuring maximum benefit to
patients whilst minimising risk.
— GSK actively supports the letter
and spirit of the law to monitor the use of a medicine and its
benefit/risk balance throughout its lifetime and proactively updates
and communicates product labeling as new information is assessed.
— GSK strongly endorses the goals of
NICE in promoting faster more equitable access to modern treatments,
the need to address post-code prescribing and the promotion of
the longer-term interest of the NHS in the development of innovative
new treatments.
— Pharmaceutical innovation is a crucial
factor in improving the quality of life. It impacts positively
upon health status, overall health expenditures and on the global
economy. Innovation should therefore be seen as a key part of
sustainable health policy. In turn, sustainable health policy
should be part of an integrated and sustainable economic and industrial
policy.
1. INTRODUCTION
TO GLAXOSMITHKLINE
1.1 GSK is one of the world's leading research-based
pharmaceutical and health care companies. The company's mission
is to improve the quality of human life by enabling people to
do more, feel better and live longer. GSK develops and manufactures
prescription medicines, vaccines, over-the-counter medicines and
oral care and nutritional health care products.
1.2 GSK has an estimated 7% of the world's
pharmaceutical market. The company has its headquarters in the
UK, where it also has a further 23 sites at which it employs over
21,000 people.
1.3 GSK invests around £2.8 billion
in R&D each year. The UK benefits from more than £1 billion
of this expenditure. GSK's global R&D organisation employs
almost 15,000 people in more than 22 sites. In the UK, GSK R&D
employs 6,000 people, 40% of the total R&D employment. Three
of top six R&D investors in the UK were pharmaceuticals companies,
with GSK the single largest UK investor.[1]
Against this backdrop the UK represents only 3.3% of the global
pharmaceutical market.
1.4 GSK contributes significantly in bringing
new medicines to patients. GSK is a world leader in the discovery
of innovative new medicines in respiratory disease, antibiotics,
HIV/AIDS, metabolic and neurological disease. These fully complement
the priorities of the NHS.
1.5 Vaccines are crucial for maintaining
public health and are one of the safest, most cost effective and
efficient ways to prevent sickness and death from infectious disease.
GSK researches, develops and supplies paediatric, adult and travel
vaccines, supplying the NHS with 20 vaccines that provide protection
against 17 diseases. (see appendix 1)
1.6 In 2003, GSK spent £338 million
supporting global community programmes, including product donation
and charitable contributions. This total expenditure was greater
than that of any other British company and included major contributions
of £500,000 to establish a children's hospital in Wales,
establishing a £1 million specialist unit for the elderly
at Ashludie Hospital, in Dundee and £1 million over four
years in support of Phase II of the new Darwin Centre at the Natural
History Museum in London.
1.7 GSK is currently the only company conducting
research into the prevention and treatment of each of the three
priority areas identified by World Health Organisation (WHO)—HIV-AIDS,
tuberculosis and malaria. In addition, GSK offers anti-retrovirals
and anti-malarials for HIV and malaria, at not-for-profit prices,
to 63 of the world's poorest countries.
1.8 GSK has contributed to the Association
of the British Pharmaceutical Industry (ABPI) written submission
to the Health Select Committee inquiry and submits the following
additional comments.
2. DRUG INNOVATION
The Development of a New Medicine
2.1 The pharmaceutical industry contributes
the majority of health care-related R&D in the UK, which is
more than all other health care research organisations combined.
Developing a medicine takes 10 to 12 years, costs over £500
million ($897 million)[2]
and is an increasingly costly, difficult and risky process. R&D
productivity is one of the biggest challenges facing the industry
today; only three in 10 medicines launched generate sufficient
sales to repay their R&D investment. To develop a medicine,
a number of sequential activities take place, as represented in
the diagram below. This process is described in more detail at
www.gsk.com.
— Candidate selection—selection
of a promising compound for development.
— Preclinical—necessary animal
and bench testing before administration to man.
— FTIM—First Time In Man—the
first study of a new compound in man; usually healthy volunteers
(Phase I studies).
— PoC—Proof of Concept—evidence
of efficacy and safety after initial patient (Phase IIa) studies.
— Phase IIb—patient studies used
to confirm the PoC and likely dose range.
— Phase III—studies in a large
population to generate safety and efficacy data for licence application.
— NDA—New Drug Application—filing
all data to regulatory bodies. (Marketing Authorisation Application—MAA
in Europe).
At each stage in this process, there is a significant
rate of compounds failing to progress to the next stage.
The Environment for R&D Investment in the
UK and Europe
2.2 Pharmaceutical innovation can be a key
element for European and UK economic growth and competitiveness
on the global market. However, European cost -containment practices
deny patients access to needed, cutting-edge medicines. Price
controls also hurt European economies by decreasing medical innovation—transferring
jobs, research, infrastructure, investment and technology from
Europe to the US.
2.3 From leading the way in R&D, the
European industry has increasingly lost ground to the US; today
more medicine development takes place in the US, which provides
an environment in which it is possible to conduct research in
well-equipped sites, with skilled well-qualified staff and appropriate
levels of regulation. There are now many emerging countries, such
as India and China, that offer a highly skilled workforce able
to operate at lower cost; companies are beginning to invest in
R&D in these countries in addition to traditional manufacturing
investments. If the UK is to retain R&D investment it will
need to remain competitive in this global marketplace.
2.4 Despite the considerable challenges
and costs relating to the R&D process, the UK still has a
thriving domestic pharmaceutical industry. The UK is a leading
location for medicines research and compares favourably with other
countries, in particular with those in mainland Europe. GSK remains
the largest investor in R&D in the UK. A major contributor
to the company's success in the UK, and a key factor in its continued
investment, is the quality of graduates and postgraduates and
the high standard of basic research carried out in the many universities
with which GSK collaborates. A thriving commercial environment
for innovative medicines is also a prerequisite for attracting
and maintaining investment.
GSK's Contribution to R&D in the UK
2.5 GSK has pioneered significant innovation
in medicines development. It is responsible for many "first
in class" therapies that have revolutionised patient care
and provided significant benefits by targeting novel receptors
and pathways.
2.6 These include the first H2 antagonists
(Tagamet® (cimetidine) and Zantac® (ranitidine)) for patients
with peptic ulcers; inhaled steroids (Becotide® (beclomethasone
dipropionate)) and inhaled short acting bronchodilators (Ventolin®
(salbutamol)) for patients with asthma; one of the earliest PPAR
agonists (Avandia® (rosiglitazone)) for patients with diabetes;
the first 5HT1 agonist (Imigran® (sumatriptan)) for patients
with migraine; two 5HT3 antagonists (Zofran® (ondansetron)
and Kytril® (granisetron)) for patients experiencing nausea
and vomiting as a result of cancer therapy, and the first nucleoside
analogues (Retrovir® (zidovudine)—AZT) for patients
with HIV.
2.7 Almost 15,000 people work in GSK's global
R&D organisation. GSK has 22 R&D facilities in eight countries
worldwide. In 2003 GSK invested almost £2.8 billion in R&D;
£1 billion of this was spent in the UK.
2.8 GSK employs around 21,000 staff in the
UK, of whom 6,000 work in R&D. GSK has R&D sites in Harlow,
Stevenage, Greenford, Ware, Tonbridge, Beckenham, Welwyn, Cambridge
and Dartford.
2.9 In a bid to increase innovation at every
stage of the drug discovery and development process, GSK has re-engineered
its R&D organisation to meet the new challenges and opportunities
the company faces. In particular, it has created a number of Centres
of Excellence for Drug Discovery, small innovative working groups
focused on specific therapeutic categories. Three of the seven
centres of excellence are based in the UK.
2.10 GSK is committed to forming partnerships
with academic institutions. The company funds research for hundreds
of masters-level, doctoral and fellowship students each year.
GSK funds more academic research in the UK than any other company.
In 2003, GSK provided funding of more than £14 million to
support UK academic based pre-clinical collaborative/Contract
Research agreements. In addition, GSK is also supporting 375 PhD
studentships—more than any other company—at a cost
of almost £4 million. In a typical year GSK funded scientists
and physicians will publish more than 1,400 journal articles and
meeting abstracts.
2.11 In a unique relationship set up with
Imperial College to develop new medicines, GSK has provided several
million pounds to support a programme which shares risks and rewards
to get molecules through to "Proof of Concept" in man.
In addition to funding, GSK is providing Imperial with access
to its chemicals and innovative platform technologies in certain
areas.
2.12 High levels of innovation take place
at the boundaries of disciplines; GSK currently provides two £500,000
endowments each year for Fellows working at the clinical/pre-clinical
interface. The GSK Clinical Fellowship scheme aims to provide
an entry into the academic career pathway for such able young
clinical scientists, at a time when entry points are difficult
to find.
2.13 Experimental medicine, the interface
between laboratory-based research and research using human subjects
is playing an increasingly important role due to the development
of new technologies such as non-invasive imaging, pharmacogenetics
and the use of surrogates and biomarkers. GSK recently announced
a unique research collaboration with Imperial College to build
an imaging centre at the Hammersmith Hospital. With insufficient
imaging capacity in the UK, this facility will allow researchers
to understand better how drugs work in human subjects; this will
be of particular relevance for cancer as well as neurological
diseases such as multiple sclerosis, Parkinson's disease and Alzheimer's
disease.
2.14 GSK has an active programme that seeks
to encourage children to study science and to pursue science as
a career. For example, more than 150 staff volunteer their time
to schools as "Science and Engineering Ambassadors"
in support of this government-sponsored programme. GSK also supports
INSPIRE, the Innovative Scheme for Post-docs in Research and Education,
a partnership between GSK, DfES, Imperial College and the Specialist
Schools Trust.
GSK's Investment in Tomorrow's Medicines
2.15 In the past four years, GSK has more
than doubled the number of candidate medicines entering Phase
I and II clinical trials; this demonstrates the high productivity
of its early phase research. At the beginning of 2004 GSK had
148 projects in clinical development, 83 of which were New Chemical
Entities, 20 were vaccines and 45 were product line extensions.
GSK will be actively working towards filing for regulatory approval
for many new products over the next few years as illustrated in
the following chart:
— MIGU—Musculoskeletal/Inflammation/Gastrointestinal/Urology.
Addressing the Issue of "Me-toos"
2.16 The term "me-too" is pejoratively
used to refer to a medicine that has a similar mode of action
to one that is already available. It ignores the nature of drug
development, which is highly unpredictable. There is no guarantee
that the first drug to market will be the best. Some new medicines
will be revolutionary breakthroughs; others will deliver incremental
benefits over existing treatments. Medicines with similar modes
of action can have significant differences in terms of their efficacy,
metabolism, tolerability and side-effects as well as duration
and magnitude of therapeutic effect. The availability of different
medicines for the same condition allows physicians to tailor therapies
appropriately to meet individual patients' needs. It also provides
therapeutic alternatives if the drug of first choice fails in
any given patient.
2.17 The range of products available within
each therapeutic class plays a key role in generating competition
between different medicines, also acting as an incentive for continuous
improvement in the product profile. Indeed, it does not make commercial
sense for pharmaceutical companies to flood markets with identical
drugs. A company's focus in R&D is to address unmet medical
needs; this may be through the development of a medicine with
a novel mechanism of action or through the development of a medicine
that offers genuine clinical advantages over existing medicines
that work through a similar mode of action.
The Critical Role of Animals in Research
2.18 GSK's huge investment in modern R&D
technologies has transformed the way the company works, and this
includes the use of animals. Over the past 10 years GSK has doubled
its R&D activity, but its use of animals has remained stable.
The company is actively engaged in research to develop and validate
experimental methods that can provide more and better alternatives
to the use of animals in research. However, at present there can
be no new medicines or vaccines without using some animals for
research and development. Animals are used where no alternative
is available and GSK aims to exceed industry standards in the
care and welfare of the animals. All animals are well cared for
by qualified, trained staff.
2.19 GSK is committed to implementing the
three Rs—Reducing the number of animals used for research,
Replacement by non-animals methods whenever possible and Refinement
of the techniques used to eliminate or reduce suffering and improve
animal welfare. In addition, GSK has added a fourth R—Respect
to ensure that appropriate care is taken in the conduct of all
its animal studies. This approach is both ethical and makes good
financial sense: animal testing is not a cheap option.
2.20 GSK has recently established with AstraZeneca
and Pfizer—working with the British Pharmacological Society,
a fund of £4 million to support animal-based in-vivo research
in UK universities. Having established this fund, GSK will work
with other funders of research including funding councils and
medical charities to co-fund a number of in-vivo capacity-building
initiatives.
R&D for Diseases of the Developing World
2.21 GSK is currently the only company conducting
research into the prevention and treatment of all three priority
areas identified by WHO—HIV-AIDS, tuberculosis and malaria.
In addition, GSK offers its anti-retroviral and anti-malarial
agents for HIV and malaria, at not-for-profit prices, to 63 of
the world's poorest countries. GSK is committed to doing more
in this area.
2.22 There is some comment about lack of
industry R&D for diseases of the developing world. The key
issue is one of market failure; in many developing nations poverty
means that no market exists for drugs that tackle the diseases
that afflict these countries and therefore there is little commercial
incentive to invest in them. This issue has been recognised and
is being addressed through a variety of public/private partnerships
(PPPs) such as the development and launch in late 2003 of LAPDAP™
(chlorproguanil/dapsone) a new anti-malarial for sub-Saharan Africa.
The initiative brought together GSK drug development researchers
with scientists in Africa and two leading UK medical schools.
GSK, the WHO and DfID jointly funded the development project.
Further information is available at:
http://www.gsk.com/about/developing_world.htm.
Recommendations
2.23 It is increasingly recognised that
to help improve the productivity of the pharmaceutical industry
in the UK and Europe, attention needs to be paid to identifying
and removing some of the barriers to innovation, where this can
be achieved without harming patient welfare. Some of those barriers
include the following:
The need to generate increasing amounts of data
before and after the approval of a new medicine
2.24 Regulatory authorities are more demanding
and increasingly risk-averse—translating into expanded data
requirements. The need to generate increasing amounts of data
both before and after regulatory approval of a new medicine is
a global issue and is a major driver of drug development costs.
2.25 Solutions could include improved dialogue
with regulators early on in drug development. Consideration should
be given to near-binding negotiated agreements on the requirements
for licensing approval, with commitments for further monitoring
and/or studies post registration where appropriate. If the nature
of a phase III programme for a medicine is agreed in advance with
the regulators and this is completed as planned with positive
results, approval should be anticipated without a post-hoc shift
in the requirements.
Increased acceptance by regulatory authorities
of biomarkers and surrogate clinical end-points
2.26 Industry is increasingly using a range
of innovative technologies in the search for new medicines. These
include novel scanning methods to evaluate disease progression,
for example in Alzheimer's disease. These technologies have led
to the development of new markers of human disease (receptors,
proteins, enzymes); such biomarkers are increasingly used to inform
development decisions by industry and have the potential to speed
the availability of medicines to patients if they can also be
used for regulatory decision making. There is a continuum from
"biomarker" (used as a development tool) to "surrogate
end-point" (sufficiently widely accepted to be used as the
clinical basis of approval). Historically, only a few biomarkers
have gained acceptability as surrogate end-points (eg blood pressure
or cholesterol levels in cardiovascular medicine). GSK recommends
increasing approvals on surrogate endpoints, especially in areas
of unmet medical need, as this would allow earlier access to new
therapies.
The difficulty of conducting clinical research
2.27 Pharmaceutical research is increasingly
focused on developing treatments for chronic and degenerative
diseases. Clinical research for such conditions is generally more
costly as more complex patient care and monitoring is required:
longer periods are needed for effects to be observed while ever
larger trial sizes are needed to establish efficacy. In addition,
there is a lack of skilled clinical scientists in the UK and infrastructure
in the public sector is frequently inadequate.
2.28 GSK recruits just 2% of its global
clinical trial subjects in the UK—this figure has been declining
due to the slow start up times and high costs for trials in the
UK. The company would like to do more clinical trials in the UK.
2.29 GSK acknowledges the Government's allocation
of more funding to NHS R&D in the Budget, and welcomes the
establishment of the UK Clinical Research Collaboration (UKCRC).
However, as a major contributor to clinical research in the UK,
the company would like to see industry play an active role in
the development of the clinical research networks. The proposal
to review both skills and training issues and the current regulatory
burden affecting clinical research in the UK are welcome.
Slow uptake of new medicines and lack of recognition
of the value of incremental innovation
2.30 One of the greatest barriers to innovation
in the UK is the slow uptake of new medicines, which also denies
access to needed medicines to patients. Research (PICTF indicator
16) shows clearly that uptake of new medicines in the UK is about
one quarter of that in the average of comparator countries one
year after launch. Even five years after launch, median UK consumption
per person is still some way below the international average.
This means that UK patients get less access to life saving or
life-enhancing new drugs. Those UK patients who do get access
to these medicines tend to get them later than they would in the
US or mainland Europe. The Government-commissioned Wanless Report
(Securing Our Future Health April 2002) illustrated how
slow uptake of new health technology could lead to poorer population
health and higher health care expenditure.
The need to control animal "rights"
extremists and to ensure there is a balance between good regulation
and a competitive environment for animal research
2.31 Animal extremism is one of the biggest
problems facing the research-based industry. GSK welcomes the
Home Office/DTI paper "Animal Welfare—Human Rights:
Protecting people from animal rights extremists". The
Government needs act to control this threat through legislative
action and effective enforcement.
2.32 Obtaining authorisation to do animal
research is more difficult in the UK than in any other comparable
country. GSK endorses the guiding principles of the UK's Animals
(Scientific Procedures) Act. However, the company believes firmly
that many of the layers of complexity and detail progressively
added to the systems of operating the Act add nothing to animal
welfare and may even detract from it. The company believes that
an extensive review is needed into the operation of licensing
procedures for animal research in the UK to improve the competitiveness
of those doing the research and to improve animal welfare.
3. CONDUCT OF
MEDICAL RESEARCH
Objectives of Research
3.1 Research aims to develop medicines that
are safe and effective in providing benefit to patients both in
treating and preventing disease. GSK recognises that all medicines
have unwanted effects and it is only the balance of the therapeutic
benefits, in the context of the seriousness of the disease being
treated, and any unwanted effects in patients that justify the
use of any medicine.
3.2 Novel therapies aim to provide incremental
benefits over existing therapies in safety, tolerability and efficacy
or a combination of all three. By improving the risk benefit ratio
of medicines, better medicines can be taken by patients and are
more likely to be taken correctly if they are tolerated well.
This allows the full therapeutic benefit to be realised for the
patient. An example of this is the development of less frequent
dosing regimens that aid compliance, such as Bonviva® (ibandronate)
for postmenopausal osteoporosis. Current bisphosphonates have
daily or weekly dosing and require the patient to undergo an overnight
fast and to sit or stand upright for 30 minutes following administration
of each dose. The once-monthly dosing regime of Bonviva® (ibandronate)
will greatly improve convenience to the patient, which should
enhance compliance with medication and ensure that patients receive
optimal therapeutic benefit.
Overview of Drug Development—Safety
3.3 The proportion of clinical studies undertaken
in the UK is declining. However, of all the clinical studies conducted
by industry and academia, industry conducts the vast majority.
3.4 The pharmaceutical industry is a clear
leader in quality, research integrity and external scrutiny, and
works closely with various regulatory authorities worldwide in
study and programme design. The results of clinical studies are
judged by the regulatory authorities in their consideration of
applications for marketing authorisations.
3.5 Safety is paramount in these considerations.
GSK has departments with the specific aim of monitoring and acting
upon safety signals in order to protect study participants and
populations. Where newly emerging data become apparent and raise
concerns, appropriate action can be rapidly implemented. GSK has
in place trained staff able to communicate rapidly and widely
with investigators; it has cancelled programmes and withdrawn
products based on such information. This accounts for much of
the high attrition rate seen in modern pharmaceutical development.
Given that unwanted effects may occur very rarely, it is not always
possible to identify these before a medicine is first licensed.
3.6 Although thousands of patients are included
in pre-licensing studies, sometimes unwanted effects occur much
more rarely. For this reason, continued safety monitoring and
Phase IV clinical trials are performed, to follow up and learn
more about the profile of medicines. As an example, GSK is spending
more than £200 million on Phase IV studies of Avandia to
examine further its profile and to generate diabetes progression
and cardiovascular outcome data in patients with diabetes. Data
generated from Phase IV studies are always submitted to regulatory
authorities, in line with Safety Assessment of Marketed Medicines
(SAMM) guidelines. These data may result in updates to the product
information.
3.7 GSK supports academic medicine to enhance
its ability to conduct research in the UK by supporting a research
infrastructure to benefit both academic and industry studies.
This is supported by ongoing work arising from the Prime Minister's
Pharmaceutical Industry Competitiveness Task Force (PICTF), an
ongoing collaboration between NHS R&D, industry, ABPI and
other interested parties such as the MHRA. GSK is an active participant
and supporter of PICTF. GSK also welcomes the outcome of the DTI/BioIndustry
Association's Biosciences Innovation Growth Team (BIGT) initiative
and the work on the UK clinical research base being taken forward
by its Biosciences Leadership Council (BLC).
3.8 GSK was encouraged by the recent announcements
in the Government's "Science and Innovation Investment
Framework 2004-2014" concerning the future of clinical
research. GSK strongly supports the Government's science and technology
strategy to restore the pre-eminence of UK research capability
and looks forward to working closely with the recently established
UK Clinical Research Collaboration (UK CRC) and the MRC/DoH Health
Research Delivery Group.
Regulation/Governance—Clinical Trials
3.9 Clinical trials undertaken in developed
countries are managed in a highly regulated environment to high
standards. These are enshrined in law with the implementation
of the European Clinical Trials Directive. Even when GSK undertakes
studies in countries outside of those whose health authorities
have agreed to these high standards, the company maintains the
same uniform standard across its development programmes. Many
regulatory agencies provide input to clinical development programmes
and will receive ongoing safety updates according to these internationally
agreed procedures. Authorities such as the MHRA will inspect studies
and the processes followed against internal company processes
and to check adherence to national standards, many of which are
now legally enforceable.
3.10 Once a study is completed, all data
are analysed according to the previously agreed analysis plan.
After analysis, a report is distributed to participating investigators
and to the ethics committee and regulatory authorities, as is
required by law. Subsequently, the data is communicated more publicly,
either through publication or presentation at medical congresses,
and frequently by both. Unfortunately when the main study hypothesis
is not proven, or no difference between treatments in the study
is seen, medical journals are often reticent to publish studies,
despite the submission of manuscripts. As a result there is an
inherent barrier to the distribution of data from "negative"
studies. In 2003 GSK produced approximately 1,400 publications
based on its preclinical and clinical research.
3.11 GSK has announced the creation an electronic
database to enable dissemination over the Internet of information
about GSK-sponsored clinical trials. The GSK Clinical Trial Register
will provide summaries of trial protocols and corresponding results
for GSK-sponsored trials of marketed medicines. In addition, the
register will provide references to publications that have appeared
in the medical literature. The register will be accessible to
physicians and the public. GSK will continue to communicate clinical
data in journals, at scientific meetings, and in letters to health
care professionals.
Recommendations
3.12 GSK recommends that the committee addresses
proposals that support the recent Research for Patient Benefit
Working Party report to enhance the competitiveness of the UK
in undertaking clinical research. Key factors that will enhance
this are to improve the UK infrastructure to facilitate the conduct
of research.
3.13 Consideration should be given to provision
of an NHS IT strategy to facilitate the identification of patients
who may be willing and eligible to participate in studies.
3.14 It has been noted that the application
of NHS Trust overhead fees and approval times varies widely across
the UK. GSK urges the committee to provide some recommendations
to standardise charges and review times to enable UK clinical
research to regain its competitiveness.
4. PROVISION
OF DRUG
INFORMATION AND
PROMOTION
Marketing and Sales Practices
4.1 GSK markets most of its products, both
in the UK and globally, through sales representatives who meet
regularly with doctors and pharmacists. New GSK representatives
are trained by GSK on the medicines they promote, the diseases
the medicines are designed to treat and appropriate marketing
practices. The training provides a thorough understanding of their
obligations and responsibilities under our marketing codes.
4.2 GSK is committed to marketing that is
ethical, responsible, and patient-centred. The company has a global
policy governing its marketing activities that applies to all
employees, suppliers, contractors and agents. GSK's policy requires
that all marketing and promotional activities are based on valid
scientific evidence, and comply with applicable laws and regulations.
The company complies with relevant industry codes of practice,
such as the International Federation of Pharmaceutical Manufacturers
Association's (IFPMA) Code of Pharmaceutical Marketing Practices,
the Pharmaceutical Research and Manufacturers of America (PhRMA)
Code on Interactions with Healthcare Professionals and the ABPI
Code of Practice.
4.3 Additional information about GSK's global
marketing practices can be found in the company's Corporate Responsibility
report and on the company website: www.gsk.com
Compliance with the ABPI Code of Practice
4.4 As stated above, in the execution of
all of its activities, GSK vigorously supports the principles
of self-regulation embodied in the ABPI Code of Practice. GSK
places great emphasis on the importance of the Code of Practice
in the training of all of GSK staff and in their day to day management.
4.5 GSK takes sanctions of the Code of Practice
seriously and believes this method of regulation is effective,
and quick in its conclusions. Breaches of the Code result in a
review and corrective action by the company; when individuals
are at fault disciplinary action is taken.
4.6 In 2003, GSK implemented a European
Promotional Code of Practice, to ensure that all staff are subject
to similar high standards to those in the UK. This GSK European
Code is extensively based on the ABPI Code.
4.7 The requirements of the Medicines Act
1968 (as amended) relating to the promotion of medicines to health
professionals and the public are fully reflected in the Code of
Practice. The Act provides criminal sanctions for breaches of
the law and the MHRA has used its enforcement powers under the
Act in serious cases. The possibility of criminal sanctions significantly
encourages support for and compliance with the voluntary code.
The voluntary code is wider in scope than the statute and is better
able to address the majority of breaches, which are usually minor
questions of interpretation, in a proportionate manner.
4.8 In addition to the Code of Practice,
GSK also ensures that its activities are aligned to other professional
codes of conduct, such as the General Medical Council's (GMC)
"Duties of a Doctor".
4.9 With regard to over-the-counter medicines,
GSK complies with the Proprietary Association of GB Code on Medicines
Advertising and the Committee on Advertising Practice British
Code on Advertising, Sales Promotion and Direct Marketing.
Information for Health Care Professionals
Pharmacists, Suppliers and Providers of Medicines
4.10 GSK provides high quality medical information
support to pharmacists, both during and out of working hours,
for emergency enquiries. In 2003, GSK handled around 12,000 medical
enquiries from pharmacists. This service is much valued by pharmacists
as it helps them to deal with many issues in medicines management,
ranging from complex pharmacology to enquiries about appropriate
dosages. A joint survey organised through the UK Medicines Information
Pharmacist Group found that on one working day 59% of NHS Medicines
Information Centres contacted a pharmaceutical company for advice.
70% of these calls were for information relating to the management
of existing or future patients, and in 47% of cases industry was
the only source of the information.
4.11 In addition to support around issues
and queries, GSK works with pharmacists through the GSK "+Plus"
scheme, to help pharmacists develop medicines management skills
and develop expertise in chronic disease management. This partnership
has recently worked well through jointly producing patient materials
and training 40 pharmacists from across the UK. This scheme has
helped pharmacists develop skills in asthma diagnosis and management,
to identify patients with inadequately controlled asthma.
Specialist nurses
4.12 The GSK Medical Information department
responded to around 9,000 medical queries from nurses in 2003.
Rapid access to scientific information is greatly valued by busy
nurses, who often do not have the time or the research resources
to find quickly the information they need for day to day practice.
Queries cover a broad range of topics, from complex pharmacological
information regarding drug interactions to information about vaccine
storage.
Clinicians
4.13 GSK provides in and out-of-hours medical
information support dealing with around 8,000 queries from doctors
in 2003. GSK also deals with reports of adverse events related
to the use of medicines and follows these up via its pharmacovigilance
department, which works closely with the MHRA and abides by all
relevant legislative and regulatory requirements.
Patients, Consumers, the General Public and Representative
Bodies
Patients and Consumers
4.14 GSK provides non-promotional information
for patients in a number of different ways. For many patients,
patient information leaflets are the major source of information
about their medicines. GSK patient information leaflets are worded
to be accurate, compliant with regulations, to be of use and benefit
to the user of the medicine and written in language that is easy
to understand. On occasions, GSK has consulted with the organisations,
for example Consumation and The Plain English Campaign, and patient
groups, over the wording of such leaflets. All patient information
leaflets are approved by the MHRA in line with the legislation.
4.15 In addition GSK has a patient enquiry
line, which last year dealt with around 1,000 medicine-related
queries from patients.
5. PROFESSIONAL
AND PATIENT
EDUCATION
5.1 GSK supports clinicians in their personal
education according to ABPI guidelines.
5.2 GSK supports junior doctors in training
for general practice and for specialist roles. This is achieved
through informal sponsorship of courses and meetings and through
formal support through a variety of schemes. GSK's "SPARROW"
programme supports Specialist Registrars in metabolic and respiratory
medicine. The programme runs with the support of clinical tutors
who select applicants presenting research at major international
academic meetings and organise educational objectives and follow
up meetings. Last year GSK supported 150 specialist registrars
in this way, allowing these physicians in training to present
their research and have the chance to interact with fellow specialists
from around the world.
5.3 GSK also supports consultants in their
attendance at independent international symposia, last year helping
180 consultants to attend such meetings in the field of respiratory
and metabolic medicine. GSK also supported approximately 150 consultants
to attend symposia in other disease areas such as neurology, urology
and HIV medicine.
5.4 GSK places great emphasis on providing
high quality educational support for specialist and practice nurses,
many of whom have little access to training funding. In 2003 GSK
funded diplomas in respiratory disease management for 235 nurses
at independent academic training institutions. For diabetes management
GSK funded 199 diplomas, 490 advanced study days and 290 other
study courses, again all at independent academic institutions.
5.5 GSK has engaged in partnerships with
independent patient groups, charities, government agencies and
other pharmaceutical companies in developing and launching disease
awareness and health promotion campaigns. An example of this was
the "out of the water closet" campaign: a project to
increase men's awareness about prostate health. This project was
developed with the Men's Health forum, the CEDC, the NHS Health
Development agency, The Prostate Cancer charity, The Orchid cancer
appeal and Yamanouchi Pharmaceuticals.
5.6 GSK has also directly accessible non-promotional
web based information to help patients increase understanding
of their disease. One such example is the Action Asthma website
www.actionasthma.co.uk, which is aimed at educating adults and
children with asthma as well as their families.
6. REGULATORY
REVIEW OF
DRUG SAFETY
AND EFFICACY
Regulatory Framework
6.1 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, and robust and bases its decisions on a high standard
of scientific evidence. Government has a particularly important
role to play in ensuring that new regulation is well formulated,
targeted and responds to a real need. The aim should be to regulate
effectively and efficiently—unnecessary over-regulation
is a disadvantage to both industry and patients. The regulatory
system should provide timely access for patients to effective
medicines, while ensuring patient safety, and stimulating research
into new treatments or technologies. GSK is committed to bringing
innovative medicines and technologies to patients and clinicians
and the GSK research agenda is driven by unmet medical need. Industry
and regulatory agencies must work together to ensure maximum benefit
to patients whilst minimising risk.
Communication between Industry and Regulatory
Authorities throughout the Lifecycle of a Medicine
6.2 There are clearly defined legislative
requirements, which necessitate communication, dialogue and the
submission of data from industry to the MHRA at various stages
in the life-cycle of a medicine. In addition, early and continuous
dialogue between companies and regulatory agencies is essential
to facilitate the understanding and introduction of new technologies
as well as the development of appropriate regulation. This is
particularly critical when there is a need to adapt regulatory
requirements eg pharmacogenetics. In light of the recent formation
of the MHRA, there are areas where closer collaboration between
the medicines and devices sector is particularly important.
6.3 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,
and information pertaining to them, 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.
6.4 It takes 10 to12 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
programme 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 patients.
6.5 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. GSK takes a proactive approach
to updating information on all of its medicines. This is demonstrated
by the fact that the vast majority of licence changes are identified
and driven by GSK. It is important that for safety related changes,
the MHRA review process does not delay the timely update of medicine
information in this respect.
6.6 Good communication channels between
the MHRA and the company is also essential when the MHRA requires
information from companies, often at very short notice eg general
safety reviews such as those relating to review of all medicines
to minimise the risk of transmission of Transmissible Spongiform
Encephalopathies or for particular classes of medicines.
6.7 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. GSK welcomes the Government's initiative to focus
on this with the set up of the Committee on Safety of Medicines
working group on patient information leaflets.
Recommendations
6.8 Where possible there should be increased
collaboration between industry and the MHRA, particularly where,
for example, patients' interests could be damaged without an effective,
data driven and co-ordinated approach including communication
eg issues related to the media.
6.9 GSK strongly supports the ongoing development
of the MHRA as a leading agency in the European regulatory agency
"network". This will require additional high quality
staff resources to achieve this and to accommodate the current
agency workload. Companies now have the possibility to select
any one of the 25 Member States to lead the assessment of their
medicines. Companies select European regulatory agencies that
not only provide high scientific excellence, but also consider
customer service and efficient performance.
6.10 GSK supports the continued representation
of industry on relevant advisory bodies of the MHRA. This link
is essential to provide input relating to the practical implications
of medicines regulation policy and feedback on the Agency's performance
from one of its major stakeholders.
6.11 GSK supports a robust and transparent
regulatory procedure, but recommends that the Health Select Committee
does not only consider MHRA transparency towards the public, as
improvements can also be identified in relation to industry. Transparency
and effective communication between the company and the MHRA during
the assessment process promotes better understanding of issues,
and ultimately results in more efficient resolution. GSK supports
any measures to ensure that the MHRA is independent of all external
influencers including any proposal to review the financing of
the MHRA if this would help dispel any perception of undue external
influence.
7. PRODUCT EVALUATION,
INCLUDING ASSESSMENTS
OF VALUE
FOR MONEY
7.1 GSK contributed to four NICE appraisals
in 2003. GSK contributes actively and openly to all NICE scoping
debates, bringing disease area, pharmacological and health outcomes
expertise.
7.2 GSK strongly endorses the goals of NICE
in promoting faster more equitable access to improved treatments,
the need to address postcode prescribing and the promotion of
the longer-term interest of the NHS in the development of innovative
new treatments. GSK has been disappointed to date by the lack
of progress in delivering these goals. Although negative guidance
can block the uptake of new medicines, there is only limited evidence
of any impact of positive guidance on prescribing. GSK therefore
welcomes the steps the Government is taking, including the appointment
of a Director of Implementation at the Institute, to improve this
situation.
7.3 To date GSK has participated in seven
initial appraisals and two reviews of guidance in a professional
and constructive manner, as outlined in NICE's guidance to manufacturers.
Particularly at the early stage of a medicine's lifecycle it is
likely that much of the evidence of the new medicine will be unpublished,
at least in full, and considerable expertise on the profile of
the medicine will rest with the manufacturer. GSK therefore believes
that the manufacturer's submission plays a vital role in informing
the discussions of the appraisal committee, however, the company
recognises the need for this evidence to be subject to appropriate
external scrutiny.
7.4 As required by the process, GSK submits
all relevant data to NICE and also provides a listing of any evidence
that GSK considers not to be relevant to the scope of the review
and why. This evidence is then also available on request. GSK
has also tried to limit the data submitted to the Institute in
confidence, as GSK understands the importance of transparency
of decision-making. GSK fully endorses the recent guidelines agreed
between the Institute and the ABPI on the limitation of confidential
information in industry submissions, and will be implementing
these in future reviews for which GSK are stakeholders.
1 DTI R&D Scorecard 2002-03. Back
2
DiMasi et al, J Health Econ, 22: 151-185 (2003); Tufts
Center for the Study of Drug Development. Back
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