The Rise and Fall of Modern Medicine (57 page)

It all started with the launch in 1984 of the acid-suppressant drug Zantac for the treatment of stomach ulcers, which would become the first ‘blockbuster' with annual sales in excess of $1 billion. Zantac was not an original drug but a ‘copycat pill', developed by the British drug company Glaxo, whose chemical structure was very similar to the first of its class, the widely prescribed Tagamet (or cimetidine) originally discovered by the brilliant Nobel Prize-winning research chemist James Black, who was also responsible for the immensely successful beta blockers for the treatment of raised blood pressure.

Zantac may have posed no threat to Tagamet's ‘market dominance', but Glaxo's chief executive, Paul Girolami, had different ideas, orchestrating a brilliant marketing campaign that would change the pharmaceutical industry for ever.
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Rather than the obvious gambit of undercutting Tagamet's price, he added a
50 per cent premium and then instructed his much-expanded sales force to promote the message that Zantac's higher cost reflected its greater efficacy. Then, in a brilliant and imaginative move that would become central to the ‘blockbuster phenomenon', he enormously widened the range of symptoms for which it might be prescribed beyond the relatively small numbers with stomach ulcers to include tens of millions troubled at one time or another with heartburn – now rechristened as the much more serious-sounding Gastro-Oesophageal Reflux Disease or GORD.

He then enlisted the Gallup organisation to conduct a nationwide survey that revealed half of Americans were troubled at one time or other by symptoms of heartburn/GORD, and recruited the star of a major television soap opera to describe how Zantac had cured her of her long-standing symptoms. And then, the crowning stone of the arch, Paul Girolami created the scientifically respectable-sounding Glaxo Institute for Digestive Health, committed to funding medical research into diseases of the gut. The beneficiaries included Donald Castell, Professor of Gastroenterology at the Bowman Gray School of Medicine, who subsequently described how Glaxo gave him $15,000 for a study in which

It worked brilliantly. Zantac's sales soared upwards to $2.5 billion to become, at the time, the biggest-selling single drug ever produced. Paul Girolami's multi-faceted marketing strategy of defining and expanding the indications for Zantac's use, creating public demand with carefully targeted publicity campaigns, and subsidising the research of prominent physicians, became the master plan that would shape the activities of his competitors desperate to find the Holy Grail of their own blockbusters.

By 1990 there were a further five; ten years later the number had risen to twenty-nine; and by 2010 there were more than 100 – twenty of which generate up to six times the revenue of Zantac in its heyday. It is scarcely possible to exaggerate the implications, not just in salvaging the fortunes of the pharmaceutical industry from ‘The Dearth of New Drugs' of the early 1980s but also in guaranteeing its future prosperity: in just three decades up to 2010 its revenues would rise a staggering twenty-five-fold.

This can be attributed, at least in part, to ‘increased volume' in meeting the greater needs of an ageing population and of the rapidly growing economies of Brazil, Russia, India and China, where during this period hundreds of millions have become sufficiently wealthy to afford to pay for medicines. Thus the pharmaceutical industry argues, quite rightly, that the rise in its revenues reflects its success in bringing the substantial benefits of modern medicines to ever more of those who need them. Fair enough; but there is another side to this coin, as that shelf-ful of books would suggest. The dramatic shift in the ethos and priorities dictated by the blockbuster imperative has resulted in ‘disease mongering' and the subversion of ‘the probity of doctors and their academic institutions'.

The term ‘disease mongering' was coined in the early days of the blockbuster phenomenon to describe the efforts of drug
companies to ‘convince essentially well people that they are sick, and the slightly sick that they are very ill' – and thus require costly drugs to make them better. Thus, New York advertising executive Vince Parry describes in a candid article, ‘The Art of Branding a Condition', his collaboration with several drug companies to foster ‘the creation of medical disorders', deploying the three main strategies of ‘elevating the importance of symptoms', ‘redefining an existing condition' and ‘developing a new condition to build recognition for an unmet market need'.
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The precedent of Glaxo's successful ‘rebranding' of heartburn as Gastro-Oesophageal Reflux Disease, as just described, suggested what might be achieved:

Several further instances of this type of ‘brand conditioning' would include ‘talking up' the physical and psychological consequences of normal physiological events such as the menopause as being sufficiently serious to warrant long-term hormone replacement therapy; medicalising normal problems such as balding, redefining common psychological traits as quasi-psychiatric illnesses, so that the common premenstrual tension becomes ‘premenstrual dysphoric disorder' and shyness becomes ‘social phobia'; and, most importantly of all, redefining the ‘limit of normal' of some physiological variable such as blood
pressure or cholesterol – thus expanding by tens of millions the numbers warranting medication to lower it.
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The scope for expanding or redefining medical conditions in these ways is obviously considerable – but the process itself has to be subtle, almost subliminal, a carefully orchestrated and protracted campaign to change perceptions or shift treatment guidelines in the ‘right' direction. This requires the help and cooperation of prominent physicians – or Key Opinion Leaders (KOLs), as they are known in the industry) – paid generous consulting fees for their authoritative opinion on, for example, the need to treat the ‘hidden problem' of ‘social phobia', or the necessity to lower cholesterol levels still further.

This leads to the further regrettable consequence of the blockbuster phenomenon: the progressive entanglement and blurring of the boundaries between the pharmaceutical industry and the medical profession when it comes to evaluating the safety and efficacy of drugs. Leading medical institutions have always played a central role in clinical trials, where the process of recruiting patients, supervising their treatment and evaluating the outcome are an important source of revenue for many academic departments. From the mid-1970s onwards the number and scale of these clinical trials rose dramatically, partly in response to the more stringent requirements of regulatory authorities such as the Food and Drug Administration but also because of the proliferation of ‘me-too' drugs like Zantac, as drug companies sought to maximise their profits by producing their own versions of already successful and established treatments.

These clinical trials, of course, had to be paid for, and as the cost escalated, so the companies sponsoring the trials had an ever greater financial interest in the outcome – as Dr Marcia Angell describes:

There are, as can be imagined, myriad ways of organising a clinical trial and editing the results so as to produce the ‘desired' result – by, for example, comparing it to a much lower dose of a competitor's drug, ‘accentuating the positive' (only publishing favourable findings) and ‘eliminating the negative' (concealing the incidence or severity of side-effects). Hence these clinical trials have an uncanny tendency always to favour the drug produced by the company sponsoring them. There are, for example, three different variants of the very profitable drug olanzapine for the treatment of schizophrenia made by the companies Eli Lilly, Janssen and Pfizer. When independent researchers reviewed all the studies in which they are directly
compared they found that in the trials paid for by Eli Lilly its drug was superior to that made by Janssen, but in the trials sponsored by Janssen its drug was better, while in those funded by Pfizer its variant always came out best.
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Dr Angell, having observed this progressive entanglement at close quarters, was prompted in April 2000 to pose the question ‘Is Academic Medicine for Sale?'
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The
New England Journal of Medicine
had for several years, she pointed out, required as a matter of policy that authors of papers published in the journal should disclose any potential ‘conflict of interest' – though ‘no-one could have foreseen how ubiquitous and manifold [they] would become'. Thus for a study comparing the value of the antidepressant nefazodone with cognitive therapy, ‘The authors' ties with companies who make antidepressants were so extensive it would have used up too much space [to publish] them fully in the journal.'
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She went on to itemise the several adverse consequences of those ever closer financial links between doctors and the industry in diverting the priorities of medical researchers away from engaging with substantive medical problems towards organizing clinical trials for which they could get (industry) funding – finding ‘trivial differences between drugs . . . [that] can be exploited for marketing'. She elaborated:

Some may be immune to such self-interest, but certainly not all, the most egregious example perhaps being the practice of those Key Opinion Leaders agreeing (for a fee) to put their names to an authoritative scientific article written by someone else in what has been described (rather convolutedly) as the ‘non-writing author, non-author writer syndrome'. ‘The syndrome has two features,' writes Dr Thomas Bodenheimer:

It is, as ever, necessary to keep a sense of proportion in all this. Modern medicines are highly effective: anti-inflammatory drugs restore mobility, antidepressants cheer people up, anticoagulants thin the blood and so on, irrespective of whether they are original or ‘me-too' drugs, or of the sharp practices involved in showing they are superior to their competitors. And doctors are for the most part honest and industrious. They might question the wisdom or rationale of the rising tide of polypharmacy – where it is not unusual for older patients nowadays to be taking half a dozen different medications. But most would consider
this ‘good practice', reflecting how comprehensively they have identified their patients' problems and initiated the appropriate treatment. They are scarcely in a position to scrutinise the findings of the thousands of clinical trials published each year, or to doubt their conclusions, nor are they likely to be aware of being ‘targeted' by those sophisticated branding campaigns encouraging them to prescribe some drug or other yet more freely.