Jeff Aronson, Honorary Consultant Physician and Clinical Pharmacologist
It is misleading to refer, as many do, to “the pharmaceutical industry”, since there is no such thing as a single industry. There are large and small pharmaceutical companies, companies that deal primarily in new compounds, in some cases specializing in biologics, companies that deal primarily in what are loosely called “generics”, companies that deal primarily in over-the-counter medicines, and small companies that spearhead investigations of new compounds before handing them over to bigger companies. However, the large companies that are at the forefront of innovation have enough similarities to warrant lumping them together under the heading of “Big Pharma”, a term that was first used at the start of the 1990s to refer to large multinational pharmaceutical companies collectively. This includes companies such as AstraZeneca, Bayer, Bristol-Myers Squibb, GlaxoSmithKline, Johnson & Johnson, Lilly, Merck, Novartis, Novo Nordisk, Pfizer, Roche, and Sanofi-Aventis. The use of the word “big” in this sense mirrors its previous use in terms such as “Big Business”, “Big Oil”, and “Big Agriculture”.
The term “Big Medicine” was originally used to describe native American medicine, but since its use as the title of a 2007 American television programme about bariatric surgery it has mainly been used to describe corporate healthcare in the USA. I use the term here to mean the UK National Health Service (NHS), its appurtenances, such as the Department of Health, NHS England, and NHS Improvement, and clinical activities being carried out in Universities.
The NHS is one of the biggest employers in the world, rivalled only, it is said, by Indian Railways, Wal-Mart, and the Chinese People’s Liberation Army. Its more than 1.7 million employees include about 370,000 nurses, 106,000 hospital and community medical and dental staff, 40,000 general practitioners, and 19,000 ambulance staff. The NHS’s current annual budget is about £116 billion, about £70,000 per employee; the drugs budget is about £14 billion. There are about 240 million patient consultations per year, of which 80% occur in general practice at about £25 each, and 20% in secondary care, at about £2800.
UK universities employ under 25% of that number: 383,000 people, of whom 186,000 are academics. Total annual expenditure is about £28 billion, about £73,000 per employee.
It is difficult to include drug companies in such comparisons, because they are disparate in nature and multinational, and UK employees contribute only part of the overall endeavour. Furthermore, many very small companies, including university spin-outs, contribute to varying degrees, for example, in early drug development, before passing on new compounds to major drug companies. As a touchstone, however, ten large multinational companies that together employ about 900,000 people spend an estimated £33 billion each year on research and development, and about twice that on marketing, total expenditure being in excess of £110,000 per employee.
The interrelations in this tripartite structure are complex. Results of research by NHS and University academics can be used by companies in drug discovery and development, and can be harnessed in spin-out companies. Academic and NHS clinicians conduct clinical studies of new compounds at all phases of development and may use the compounds as tools in their own research. They sometimes act as consultants to companies, advising on aspects of development. Academics also advise regulatory agencies, such as the Medicines and Healthcare products Regulatory Agency (MHRA) and the National Institute for Health and Care Excellence (NICE), about the acceptability of the medicines in clinical use, and teaching other doctors and students. Typically, however, rules about competing interests bar individuals who work closely with pharmaceutical companies from participating in the work of regulatory agencies.
Improvements in these interrelations are possible in several areas. Here I discuss four: drug discovery, transparency, funding, and public understanding of medicine.
Erstwhile methods of drug discovery, which focussed on biological systems, have given way in recent years to an intensely target-driven process, which has been called ‘targetophilia’, and ‘targephilia’, but for which a better word may be ‘stochophilia’ (Greek στόχος = “aim”). Aiming at single targets (e.g. specific receptors and their subtypes) was fruitful in the past and continues to be, but less so than before. It is not, I believe, coincidental that in recent years the number of failures in drug development, particularly during phase 2, has increased. It has been estimated that success rates during phase 2 in large pharmaceutical companies fell from 28% in 2006/7 to 18% in 2008/9. In one survey of 108 compounds, 51% failed because of lack of efficacy. Furthermore, many companies have disinvested in areas previously thought to be potentially fruitful. Both pharma and the universities could consider the potentially beneficial effects that could accrue from a return to a systems-driven approach, and a search for innovative medicines with multiple mechanisms of action. This could be facilitated by the establishment of Institutes of Drug Discovery and Development, whose activities could include development and implementation of translational pharmacology research. They could also draw on the collective expertise of academic clinicians and scientists, while liaising with corporate partners to facilitate collaboration, knowledge transfer, and effective translation.
Changes in societal attitudes to transparency have markedly affected the relationship between Big Pharma and Big Medicine over recent years. Companies have, in some cases, withheld evidence that might adversely affect perceptions of the benefit-to-harm balance of a medicine. This has started to change with advance registration of trials and declarations, and some companies have agreed that they will make all the evidence available and have individual patient data scrutinized in clinical study reports collected during randomized studies. This has also been extended to transparency in animal experimentation by groups such as CAMARADES. The All Trials campaign, to which nearly 90,000 individuals, and over 650 organisations have subscribed, has been instrumental in pressing for increased transparency. Another aspect of this is the stated willingness of some companies to declare moneys paid by them to named healthcare professionals. All this should be universal.
From time to time companies have funded training posts in universities, but these have declined in recent years for financial reasons. The disparity between funding of drug companies and universities, however, is enormous, while the latter punch way above their weight in contributing to drug discovery. Major drug companies should be prepared to fund academic posts, as I have previously discussed in the wider context of academic medicine (see Figure).
Figure Possible joint funding streams for different types of clinicians, researchers, and teachers; the illustrated possibilities are not comprehensive
Particularly pressing is the need for basic and clinical pharmacologists, who have in the past been instrumental in drug discovery, facilitating decision-making during drug development, and introducing new therapeutic applications (e.g. the use of beta-blockers in hypertension, first described by Brian Prichard, and of cysteamine and acetylcysteine in paracetamol overdose, pioneered by Laurie Prescott). Meanwhile, the detecting, reporting, and interpreting of adverse drug reactions, and the teaching of careful, safe, and effective use of medicines remain pivotal. Currently in the UK there is about one consultant academic clinical pharmacologist for every million of the population; the contrast with other countries is striking—for example, in Croatia the ratio is about one to 150,000. Many of those who hold the title of clinical pharmacologist in pharmaceutical companies are not clinically qualified, and although this is not a huge disadvantage in the early phases of drug development, it becomes problematic in later phases. Companies should seek partnerships with universities in training clinical pharmacologists. Secondments for longer periods than have been usual in the past—e.g. five years, rather than one year—would be mutually beneficial. For their part, the universities should seek to have the restrictive influence of research assessment exercises waived for individuals who are seconded, to encourage fruitful academic career paths when they return to academe. Some among those who are seconded will choose to stay in the companies anyway.
The NHS is in a financial crisis and cannot currently afford to take part in the large high-quality clinical studies that are necessary for successful drug development. Drug company funding, aimed at training clinical trialists in the provision of hospital-based clinical investigation units, could help mitigate this. The increasing tendency of drug companies to fund work of this sort abroad, more cheaply purchased, has militated against such developments in the NHS. More funding of research in general practice could be achieved by funding GP trainees to do clinical research. Different types of clinician–researcher–teachers, independent of drug companies, could be funded through different types of collaborations involving corporate partnerships.
The whole purpose of all this is, of course, to serve patients and provide them with medicines for which the benefit-to-harm balance is highly favourable. Patient’s expectations of the benefits that medicines can bring have increased markedly in recent years and adverse reactions have become less acceptable. Nevertheless, patients are still not well informed in this area. Drug companies should seek to provide clear patient information, moderated by independent academics, rather than by company members. This also applies to the education of general practitioners. Most teaching and training in therapeutics and prescribing occurs in hospitals, but 80% of all prescribing occurs in general practice. Better education and information should also allay the fears recently voiced about the sharing of patient data, through large databases, with drug companies.
However much Big Pharma is feeling the financial pinch, UK Big Medicine is much worse off. The former should be giving more unrestricted, no-strings support to the latter, pursuing the common aim of discovering innovative, clinically effective, and cost-effective medicines, while also galvanizing healthcare.
An earlier version of this article appeared in Pharmafield (http://www.slideshare.net/AmySchofield/dec14-43584038)