Select Committee on Health Minutes of Evidence


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 past—for 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 industry—in 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 studies—many 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 IRESSA—the 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 patients—particularly 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) Report—Performance 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 expertise—we 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 HCPs—Doctors, nurses, pharmacists—who 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 areas—pharmaceuticals 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 guideline—By 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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