For the first 25 years of my medical career, I didn’t buy a pen. Free writing implements were in plentiful supply at every educational event I attended, dished out by drugs reps and emblazoned with the names of their latest products. Then there was the medical kit: when taking blood, I still use a tourniquet bearing the name of a once-popular heart failure treatment. More gimmicky items included cuddly toys and stress balls. My now grown children still recall their excitement when Dad came home bearing pharmaceutical goodies for them.
The purpose of these inexpensive gifts was to build and maintain brand awareness. When using a peak expiratory flow rate calculator to assess the severity of someone’s asthma, for example, the odds were I would prescribe the inhalers made by the company that had given me the tool, the names of which were handily inscribed there as an aide-memoire. More challenging for the pharmaceutical industry was how to penetrate the world of medicine with new products.
Developing a new pharmaceutical product is expensive, involving multiple trial phases of increasing size and complexity: the Association of the British Pharmaceutical Industry estimates the costs to be more than £1bn per drug. It is also time-consuming, taking ten to 15 years from identification to market launch. This chews up at least half of the 20 years of patent protection, leaving the company less than a decade of monopoly sales during which to recoup costs. Once a patent expires, other companies can market the drug in non-branded form. These “generics” can be as much as 90 per cent cheaper than the original product, reflecting the costs of manufacturing and distribution with none of the R&D overheads.
Small wonder, then, that pharmaceutical companies are compelled to achieve maximum market share in as short a time as possible once a drug is licensed. Research papers published in journals are generally too cumbersome to create rapid, widespread change in practice, and adverts are easily skimmed past. The industry traditionally relied on teams of reps speaking directly to prescribers, but doctors are busy people, shielded behind secretaries and receptionists, and drug companies are legion. How could the rep from Pharma A beat the competition from Pharmas B-Z?
This conundrum led to an arms race that was very much in evidence in the early years of my career. Colleagues were treated to hot-air balloon flights over Oxfordshire by one enterprising rep. Meals out at swish restaurants were commonplace. Fancy attending a conference being held at a desirable ski resort? No problem – all expenses would be paid. Industry codes meant these jollies were supposed to contain educational content, but that was beside the point. They served to create indebtedness. The next time a rep sought an opportunity to pitch their company’s wares, their earlier largesse made it more likely they would be granted an audience.
Did it work, this dubious dance between pharmaceutical industry and medical profession? The short answer is yes, otherwise companies would not have invested so heavily in their sales forces’ expense accounts. The slightly longer answer is that once one company was mounting an effective field operation, its competitors had to follow suit or risk falling behind. Expansively solicitous direct-to-prescriber marketing was as much about staying in the game as it was about gaining an advantage over other players.
Was it harmful? The answer to that is multifaceted. Advances in therapeutics over the past four decades have transformed the outlook for many patients. People survive diseases that would have been routinely fatal in my early career; symptoms that might make life intolerable can often be controlled; complications that occur over time can be prevented or mitigated. There is a clear benefit in busy doctors being kept updated with the latest developments. The biggest problem lies in the fanfare of claims that invariably accompany the launch of a new drug.
Reps, designated only a few minutes to make their pitch, will inevitably focus on key take-homes: how effective a product appears to be, how minimal the side-effects. But history has repeatedly taught us that the downsides of drugs often become clear only once they enter wider use. I still recall the enthusiastic endorsement of the rep who, in the mid 1990s, came to tell us about a wonder drug for acid reflux called cisapride. Within a few years, its licence had been suspended because of fatal effects on heart rhythm. I’d never actually prescribed it – but that wasn’t true of rofecoxib, an anti-inflammatory for arthritis, which later proved to increase risk of stroke and heart attack. Then there was sibutramine, a highly effective appetite suppressant – the Ozempic of the late Noughties – which several patients came to plead for on the strength of hyperbolic media coverage. It too was taken off the market because of emerging evidence of adverse cardiovascular outcomes. These and other experiences reinforced for me that, when it comes to drugs, there is great merit in being a “late adopter” – wary of the chutzpah surrounding apparent medical breakthroughs, preferring to wait and see how things turn out in practice before exposing one’s patients to relatively untried treatments.
Still, I must acknowledge that those congenial relationships with pharmaceutical reps must have exerted some influence on my practice. Pally reps making return visits would be pleased if they heard I’d been trying out a new drug. Conversely, I remember the awkwardness if I had to confess I had yet to give it a go.
The jamboree ended abruptly in 2012 with the enactment of the Human Medicines Regulations (HMR). These prohibited drug companies from providing any gift or other benefit to healthcare professionals in connection with the promotion of medicinal products unless “inexpensive” and relevant to the practice of medicine or pharmacy. No more hot-air balloon flights from then on.
The Association of the British Pharmaceutical Industry reacted counter-intuitively, updating its code of practice even more stringently to ban marketing materials of any sort. Reps began hurriedly offloading stacks of branded Post-It notes and pens they would soon not be permitted to deploy. But by this time, drugs companies had realised that there were more productive methods on which to focus their attentions.
The National Institute for Health and Care Excellence (Nice) was established in 1999 to eliminate the “postcode lottery” that bedevilled the NHS. Access to treatments and services depended on decisions made by local health authorities – where you lived materially affected what healthcare you might receive. Over the course of its 25-year existence, the public body has methodically compiled and maintained an enormous bank of guidance concerning what the health service should offer for an ever-expanding range of health conditions.
One of Nice’s key roles is assessing the place of new drugs or devices coming on to the market. Things got off to a bad start from the pharmaceutical industry’s perspective. Nice’s very first appraisal was of a treatment for influenza, Relenza, which it judged insufficiently cost-effective to mandate use across the NHS. The decision outraged the manufacturer, Glaxo Wellcome, which threatened both judicial review and withdrawal from the UK. When those tactics failed, it appealed to the then prime minister. Tony Blair declined to intervene, insisting that Nice was independent of government and politics, and must make its determinations unhindered.
Just as the pharmaceutical industry learned early that a “no” from Nice would scupper its chances of a product being adopted, so too it has subsequently understood the enormous power of a “yes”. No longer does rapid uptake of a new drug depend on the efforts of a sales force trying to persuade prescribers piecemeal. If Nice approves a treatment, the NHS is required to make it available, typically within three months. It is like having a rep pop up simultaneously in every consulting room and on every ward around across the country, but without the need to make the case for their product. The rapidity with which novel drugs get rolled out maximises a company’s earnings during those precious years of patent protection. It is a pharmaceutical executive’s dream.
There are still knock-backs – witness the outcry over Nice’s refusal to endorse Leqembi, a drug that can, at enormous cost, briefly slow the progression of Alzheimer’s disease in those patients who avoid its toxic and sometimes fatal side-effects. But overall, the industry has found Nice, well, a nice body with which to do business.
The chance of a positive adjudication is greatly enhanced by familiarity with its decision-making processes. There is a magic number – the “cost per QALY” – that supposedly encapsulates the anticipated gain in “quality-adjusted life years” versus the price the NHS is expected to pay. It would be a very dumb pharmaceutical company that submitted a proposal to Nice without having carefully prepared its case – including enumerating every conceivable QALY gain, and determining the upper limit of what it might reasonably be able to charge. If a pharmaceutical company can present plausible figures that show its product coming in below Nice’s cost-per-QALY threshold, it is virtually guaranteed success.
The industry has learned other tricks besides. What matters to patients (and should matter to their doctors) is whether a treatment improves how they feel, how they function and, in the case of life-limiting diseases, whether they survive. These are called clinical outcomes and used to be the gold standard in randomised controlled trials. But such trials take a long time to conduct and are costly, both directly and in terms of lost patent-protected years. Over the past three decades these gold standards have been increasingly replaced by surrogate end points in medical research – does a drug lower blood pressure, shrink tumour size, and so on – which can be studied much more quickly. The assumption is that these changes will equate to improved clinical outcomes, but that is by no means a given. There may be no real-world benefit to patients, or the drug might actually cause net harm (the reason some pharmaceuticals end up being withdrawn within a few years).
Nice is the very definition of an “early adopter”, promoting the wholesale prescription of novel drugs throughout the NHS. It is also prone to wishful thinking, extrapolating treatment recommendations to groups of patients or clinical scenarios beyond those the evidence base supports. As a late adopter, I find myself ever more at odds with the direction Nice is pushing clinical practice. Its recent decision to advocate the roll-out of the weight-loss injection Mounjaro is a case in point. We know the jab reduces BMI for the duration of treatment, but we have no idea if this does patients any long-term good. It will not surprise me if at least one of the new crop of anti-obesity drugs gets pulled in the years ahead due to as yet undetected adverse side-effects.
Nice has no regard for opportunity-cost. Each new treatment is evaluated in isolation, as though it can be inserted seamlessly into NHS activity without causing so much as a ripple. Such is the pace and scale of pharmaceutical development, we have entered an era in which the constant stream of new products – for each of which a plausible “business case” can be made – is far outstripping the health system’s capacity to provide them. We must urgently establish processes that weigh the relative values of interventions: if we decide to start providing this drug, what will we have to stop doing instead, and is that the best use of the resources we have available?
Nice’s vaunted independence may already have become subject to political influence. A year-long investigation published by the Pharmaceutical Journal in 2023 into the roll-out of a cholesterol-lowering injection, inclisiran, found evidence of “highly unusual” pressure being exerted by officials in NHS England and the Department for Health and Social Care. Nice had been inclined to restrict the jab to research purposes only, and to wait until further trials had confirmed positive outcomes for patients. This evidently threatened an agreement between the government and Novartis, owners of the inclisiran patent. Ministerial imperative was invoked, and inclisiran appeared in Nice’s guidance. (Novartis has stated that its inclisiran roll-out has been delivered in line with all regulatory protocols and requirements.)
Politicians largely aren’t influenced by hot-air balloon flights; their vulnerabilities are altogether different. They are readily attracted by opportunities to announce “game-changing” initiatives that appear to demonstrate decisive dynamism. Then there is the unquenchable thirst for economic growth. It is unknown how persuaded GPs will be by the evidence base for Mounjaro. Meanwhile, Eli Lilly, the manufacturer, is committing £279m to UK life-sciences research – one of the successes trumpeted at the International Investment Summit convened in October by the Labour government.
Wes Streeting, the Health Secretary, is frequently to be heard extolling the NHS’s potential, as a comprehensive single-provider national healthcare system, as a proving ground for new treatments. The UK is fast becoming the world’s favourite pharmaceutical trials population, turbocharging our already problematic early-adopter status.
Streeting has clearly been seduced by the chimera of predictive “personalised” medicine – the idea that genomics and Big Data can together create a crystal ball in which to foresee a person’s future health conditions and enable something (invariably pharmaceutical or technological, and therefore economically productive) to be done to prevent them. As the University of Utah professor of philosophy James Tabery describes in his 2023 book The Tyranny of the Gene, this idea has already been tested to destruction in the US. So much of disease in the developed world is determined not by our biology, but by the ways in which our biology is affected by our socio-economic environment. The UK seems destined to divert itself for yet more decades chasing a modern-day myth.
The pharmaceutical industry has developed other ways of enhancing demand for its products. Numerous industry-funded and resourced initiatives can now be found throughout the NHS, ostensibly concerned with case-finding new diagnoses of sub-clinical disease, or identifying individuals who might be deemed at risk of ill-health in the future, or maximising treatment of those with established conditions. Not infrequently, such initiatives run counter to advice from the UK National Screening Committee (UK NSC), the role of which – ensuring the NHS only involves itself in programmes that have clear advantage to patients – is being increasingly undermined.
Other alliances are contributing to escalating drug prescription. Over the past 20 years there has been an explosion in the numbers of disease-orientated charities and patient groups, which frequently rely on donations from industry – all publicly disclosed – for substantial amounts of their funding. These special-interest organisations, invariably animated by unimpeachable motives, exert lobbying pressure on government, Nice and the UK NSC that can only be helpful to the pharmaceutical industry’s balance sheets. The controversy over screening for prostate cancer (for which there is at present no scientific evidence of clinical effectiveness, and considerable evidence of net harm) is being driven by just such third-sector agitation.
The relationship between the pharmaceutical industry and the NHS must be viewed through multiple lenses. Life sciences have been responsible for extraordinary progress in our ability to cure, treat and mitigate many health conditions that in previous generations would blight and truncate lives. Yet commercial pressures all too easily generate unwise and injurious decisions – whether that be among doctors, regulators, civil servants or politicians.
We badly need a reset: a renewed respect for the potential for drugs to cause great harm as well as good, and a marked deceleration in our headlong rush towards the next big thing. One simple bargain would alter the landscape immeasurably: in return for an extension in the patent period for new pharmaceuticals to, say, 30 years, we should once again require drug companies to conduct proper trials into whether their products create meaningful clinical outcomes. And Nice should be given a statutory duty to call out and resist political influence on its deliberations.
These are not UK-specific problems. Robert F Kennedy Jr, appointed by Donald Trump to lead on health in his administration, has identified a comparable “capture” of the drug regulatory apparatus by the pharmaceutical industry in the US as a key target for reform. While Kennedy’s views on vaccines are distinctly questionable, in this analysis – and in his professed determination to tackle the ill-health being driven by the food industry – his instincts are correct. We need to control the malign outcomes commercial imperatives can all too easily engender. There is no such thing as a free pen.
[See also: Picasso’s mistreated muses]
Content from our partners
This article appears in the 10 Apr 2025 issue of the New Statesman, Spring Special 2025