1.  The College welcomes the opportunity to submit comments on the terms of reference and other issues relevant to the new Inquiry announced by the House of Commons Health Committee.

  2.  The Royal College of General Practitioners is the largest membership organisation in the United Kingdom solely for GPs. It aims to encourage and maintain the highest standards of general medical practice and to act as the "voice" of GPs on issues concerned with education; training; research; and clinical standards. Founded in 1952, the RCGP has over 21,500 members who are committed to improving patient care, developing their own skills and promoting general practice as a discipline.

  3.  The College is willing to give oral evidence to the Committee if requested.

  4.  The issuing of a prescription is, after the consultation itself, the commonest intervention the health service has with the patients it serves. A significant proportion of the population receives at least one prescription on an annual basis and the vast majority of the population receives at least one prescription in any five year period. Therefore the Health Service and the pharmaceutical industry have a valid shared interest. In the year to April 2003, 650 million prescriptions were generated from general practices in England. Although the NHS is a major consumer of pharmaceutical products, we have to recognise that globally, NHS consumption is relatively insignificant.

  5.  It is vital that the Health Service interacts and communicates constructively and strategically with its major supplier, the pharmaceutical industry. The relationship between the Health Service and the pharmaceutical industry must mature and become more strategic if there is to be greater influence on the future direction of drug research, the methods of drug provision and utilization and the re-establishing of the UK as a premier site for drug innovation and development. There are linked benefits for our population of patients, the academic and clinical sectors and the economy as a whole (the pharmaceutical industry being the third biggest "earner" for UK plc behind tourism and the City). The development and implementation of new drugs is a vital part of the overall public health strategy for the UK.

DRUG INNOVATION AND DRUG RESEARCH

  6.  There is evidence the pharmaceutical industry is moving its research and development to other health economies outside the UK. The reasons are many and complex and include:

—  Tax regimes.

—  The high level of opposition to testing in the UK from extremist animal rights groups.

—  The complex and often conflicting demands of legislation (particularly the over restrictive interpretation of legislation on data protection and confidentiality of medical data to restrict population based research).

—  The poor information and IT infrastructure of the UK health service.

—  The fragmented and customer un-friendly nature of academic units and clinical services. Multiple layers of Research Ethics approval may be required and a disparate, and sometimes competing, collection of clinical and academic teams may need to be brought together to achieve sufficient mass for such research. Such broad based collaboration between units is not adequately recognized and rewarded currently by our clinical academic and research bodies and therefore there is a disincentive for individuals to participate in such networks. However, much modern clinical research requires large numbers of subjects and locations, and therefore requires large, well organized and efficient research networks. Other countries are forming networks of clinicians and researchers who then can go out and compete collectively to be commissioned by the pharmaceutical industry for this research business.

—  The poorly rewarded academic and insecure career structure for clinical academics results in many dropping out of this career and the best being attracted overseas by more attractive working conditions and remuneration packages.

  7.  The UK will fall even further behind in competing for this international research business if it does not urgently recognize the issues around genetic research and establish a legislative and organizational framework that recognizes and protects the interests of the patients, the researchers and the pharmaceutical industry.

  8.  A healthy and robust research environment in the UK retains excellence in the UK and stimulates development and improvement in clinical practice. It directly benefits patients by developing new treatments and making them available earlier (and when in trials often in a subsidized format) for the population of the UK.

  9.  The development of a strong and vibrant pharmaceutical industry in the UK working in partnership with the Health Service allows two way exchange of ideas. It allows the health service to influence the direction and nature of pharmaceutical research, and encourages the pharmaceutical industry to align its strategies and practices to those of the NHS.

  10.  While there will, quite rightly, be much to consider about the positive aspects of the pharmaceutical industry, there can be a negative influence where there is no research and development because the industry does not believe there is a good market. This is illustrated by influenza and neuraminidase inhibitors: influenza research, both epidemiology and treatment, was greatly enhanced by the discovery of neuraminidase inhibitor drugs but this was carried out because the industry thought that there was a large market for it. That did not turn out to be the case—and while we have an important new class of drugs (which will be very relevant should a pandemic occur)—had the industry anticipated the lack of market demand it could not have been expected to take on the initiative.

  11.  We welcome the very real therapeutic advances that have been made in recent years but we regret the large number of expensive "me-too" drugs which offer no genuine improvement and seem to be produced merely to enable different companies to gain financially on each major advance. As an example of this sort of practice, we would refer the Committee to the following point made by Andrew Herxheimer in the most recent edition of the Drug and Therapeutics Bulletin: "A company introducing a new drug aims to achieve high sales rapidly to recoup the research costs quickly. To persuade prescribers to try the drug, they must be offered impressive advantages—typically high effectiveness and simple usage. An early response to treatment reinforces the prescriber's decision, and is more likely at a higher than a lower therapeutic dose. Low doses that might be effective in fewer patients are not developed. Drug companies are not required to provide data on the lowest effective dose or to produce low-dosage forms. So, often, patients receive higher doses than they need."

  12.  It would also be fruitful to look into the increase in "disease-mongering" (see British Medical Journal's theme issue of April 2002) and the medicalisation of normal human variation into normal and abnormal, with the interest of the pharmaceutical industry in seeing an increase in the "abnormal" population who need drugs for one reason or another. We are concerned about those disease conditions which lie at one end of a biological continuum—examples include hypertension, hyperlipidaemia, osteoporosis, anxiety, depression. It is always very difficult to draw a line and dichotomise a continuous variable into normal and abnormal categories but it is very much in the interest of the pharmaceutical industry to draw a line which includes as large a population as possible within the range of abnormality. However, it is almost certainly not in the interests of patients or citizens. A paper in press at the Scandinavian Journal of Primary Care looks at the 2003 European guidelines on cardiovascular disease in the context of the Norwegian population which is one of the world's healthiest and longest living populations. Implementation of the current guidelines would lead to identification of one or more "unfavourable" cardiovascular risk factors in a large majority of the population, including more than nine out of 10 individuals aged 50 years and older. We ask in whose interest are such guidelines operating and point out the huge and increasing burden on publicly funded health systems which result from this level of intervention. If current trends continue, publicly funded health care systems will be at risk of financial collapse and the principle of inclusive health care may be lost with huge costs to society as a whole.

  13.  This can also increase health inequalities both nationally and globally. Nationally, in rich countries like the UK, only a minority of the population is acutely ill at any one time whereas the majority are healthy and can be persuaded of a need to take action to remain so by undergoing screening and taking preventive medication. As the overall health of the population increases, there is more money to be made out of selling health care interventions for the healthy majority than for the sick minority. More money is now invested in research into the prevention of disease than into its treatment—which serves to divert investment away from the sick towards the well, away from the old towards the young and away from the poor towards the rich. Similarly, the excessive consumption of medication, particularly preventive medication, in richer countries is a powerful driver of global health inequalities because there is much more profit to be made from developing and selling medication to the rich and well than to the poor and sick. This is frighteningly well illustrated by the response of the pharmaceutical companies to the AIDS epidemic in Africa. And there are also some dangers for the rich. Excessive prescribing drives iatrogenesis to the extent that 28% of US hospital admissions of older people are estimated to be caused by a drug related problem with significantly more being the result of adverse reactions than of "non-compliance". Too often a prescribing cascade is set in motion whereby the side effects of one drug produce a new health problem and so a second medication is prescribed, which in turn produces a new symptom and the need for a third medication. The pathway that leads from osteoarthritis to a NSAID to mild hypertension to a thiazide diuretic and on to diabetes and/or gout is but one example. The over-consumption of pharmaceuticals is a serious and growing health problem.

THE PROVISION OF DRUG INFORMATION AND PROMOTION

  14.  The health service must influence the nature and extent of pharmaceutical promotion to clinicians and the public. Joint codes of conduct should be developed between the pharmaceutical industry and NHS organizations (Primary Care Trusts and Hospital Trusts) detailing the standards of behaviour of the pharmaceutical industry representatives and health service staff. Examples of such understanding already exist (eg Hillingdon PCT code of conduct for interactions with the pharmaceutical industry) and have been effective in discouraging the worst excesses of practice.

  15.  The Committee might wish to consider the influence of the pharmaceutical industry on patients' organisations and on the pressure to implement "Direct to Consumer" advertising in Europe and the balance between genuine information to patients on the one hand and advertising and health promotion on the other. Attached to this memorandum is a paper ("The influence of the pharmaceutical industry on patients' organisations within Europe") written by Dr Iona Heath for the British Medical Association's European Forum in her capacity as the Royal College of General Practitioners' representative on that group.

  16.  Patient Information Leaflets (PILs) are often effectively written currently to minimize the legal exposure of the pharmaceutical industry. Therefore their potential role to inform and educate the public is not fully exploited. The whole issue of the provision of unbiased informative and understandable information to clinicians and the public needs to be addressed and this should be considered by joint working groups of the health service, the public, and the pharmaceutical industry. It would be preferable for PILs to be written by sources independent of the pharmaceutical industry and should emphasise the place of the particular drug in the overall scheme of disease management.

PROFESSIONAL AND PATIENT EDUCATION

  17.  Much postgraduate GP education is funded directly or indirectly by the pharmaceutical industry. Their involvement is heavily regulated and the vast majority of such sponsorship and funding is carried out in a professional and non-promotional way. However, the Committee might like to consider the current over reliance placed on pharmaceutical funded education (eg multi sponsorship of patient groups such as Asthma UK) and what the consequences might be for research and education if the industry did not provide so much funding in the future.

REGULATORY REVIEW OF DRUG SAFETY AND EFFICACY

  18.  The UK requires a large database of routinely collected clinical information to act as a quick response database for drug safety queries. The population to be covered would need to be at least 2 million; it could be a by-product of the electronic patient record. It would allow regulatory authorities, for instance, to rapidly double check drug safety concerns in weeks or months rather than the years required for a specially designed and constructed prospective study. An example of an occasion on which such a database could have been used rapidly and with great success is the third generation combined oral contraceptive scare.

  19.  The reporting of adverse drug events and safety data must be extended very significantly and updated to recognize and include the potential of the electronic patient record and the computerization of patient information systems and clinical notes.

  20.  The potential impact of genetic medicine must be recognized and prepared for by both the health service and researchers.

  21.  The question of efficacy has traditionally dominated the issue of cost-effectiveness; while NICE is redressing that balance, the next issue must be long term effects on individuals, groups and society as a whole. That will be even more challenging. For example, HRT, if invented now, would be regarded as both efficacious and cost-effective in the short/medium term for individuals and the population; but the longer term effects on individuals and society (given what we know now) might mean that the decision to introduce or recommend HRT would be much more balanced.

  22.  This argues for Phase 3 and post-marketing research to be independent of the pharmaceutical industry and for evidence to be systematically collected on all major types of drug over sustained periods after introduction.

  23.  If the UK becomes more directive over such matters, the pharmaceutical companies will threaten (again) to leave the UK. There is therefore a balance between rational dissemination and evaluation of innovation and the interests of the pharmaceutical companies (and of the UK economy), and that balance should be explicit.

  24.  Increasingly the regulatory and cultural climate in the UK mitigates against big second and third phase drug trials which are increasingly being carried out in Eastern Europe or third world countries. There are significant ethical issues there.

PRODUCT EVALUATION, INCLUDING ASSESSMENTS OF VALUE FOR MONEY

  25.  Current evaluations are severely limited and biased. They are essentially dominated by papers published in peer reviewed papers, where it is already known that there is a bias to positive results rather than negative results, and towards the specialist secondary and tertiary setting rather than primary care and where there is an under-representation in the research of the elderly, the young, pregnant women, and ethnic and cultural subgroups. The current use of the double blind random controlled trial can see the results being controlled in some way by the company supporting the research and the possibility that negative results are suppressed.

  26.  The economic evaluations are frequently severely limited and over simplified. They are not sufficiently extensive and long term to recognize adequately the impact of service redesign, opportunity costs and benefits and the impact of secondary disease or concurrent diseases (ie by preventing a fatal myocardial event a patient may then go on to develop vascular dementia, require anti-dementia drugs, need long term residential and nursing care, and a hip replacement for his oteoarthritis, before eventually dying with prostatic cancer.

August 2004