Pharmageddon. David Healy

but here let us focus on the doctor before he walks into the showroom.

      He will likely think he is not particularly influenced by the ads for drugs he sees. And in this he is undoubtedly correct to a point—at least three-quarters of the ads for a drug are not aimed at him. He may even think that most ads make him less likely to prescribe rather than more likely. He will be unaware that just as marketers distinguish between women and men, or between those of us who want high-tech versus retro running shoes, so they also have learned to distinguish between “high-flyers,” “skeptical experimenters,” “rule bound,” and “silent majority” doctors.¹⁸ Few doctors have any idea how the marketers have pigeonholed them and as a result will not be able to pick out the ads aimed at them from the ones aimed at others that serve a secondary function of throwing any particular doctor off the scent.

      High flyers are the doctors keen to try new things. They don’t want to hear what is in guidelines or what colleagues are doing. They are interested in the latest reports that promote a drug for something new, or in a different cocktail with other drugs, or in a higher dose than previously recommended. These are doctors that companies term “early uptakers” and they are important to getting a new product adopted. Skeptical experimenters are similar but more likely to temper their prescribing practices on the basis of experience.

      In contrast to these two types, marketers identify most doctors as either rule bound or silent-majority conservatives. For the rule bound, regulatory approval of a drug means the drug should be used for the stated purpose and for that purpose only, and in accordance with the latest guidelines. The conservative majority want everything kept simple. They pick a drug and stick to it; they’re most interested in aspects such as whether the drug comes in a new formulation that might enhance compliance—a tablet that dissolves instantly in the mouth, for example, so that patients cannot but comply.

      Where doctors, the media, and others see a salesperson visiting a physician with free pens and an offer of lunch, with a pitch based perhaps on the results of some recent clinical trial on a drug, the key exchange is of a different order: it is not what is handed over to the doctor but how he or she responds to various probes and what is then fed back to the company. After that, the pitch to a high flyer will be as different as the one to a rule-bound doctor just as a car salesman’s pitch is different to someone keen to buy a sports car compared to someone who wants to buy a family car.¹⁹ The ads and the patter directed at high flyers will show a doctor on a mission to tackle the scourge of disease, a mission that sometimes justifies extreme measures, where the ads to the rule bound may feature the latest authoritative guideline. The idea is to get the mood music right in the showroom, to get the brand speak in the right tone of voice.

      Doctors won’t have to make their own way to the showroom—they will likely be transported there even if the showroom is in a different country, being wined and dined en route. Once in the showroom, a doctor won’t meet a salesman but instead, colleagues, or a local professor, or some medical eminence. The knowledge needed to construct a blockbuster brand is derived almost entirely from the physicians to whom the product is being sold. The careers of Lipitor, Nexium, Vioxx, Prozac, and Depakote make this clear. Doctors tell the company what they, the doctors, want to hear.

      In the course of a drug’s development, panels of medical academics— opinion leaders—are convened to see what the consumer wants. Pharmaceutical companies do nothing so crude as call these focus groups, but this is essentially what they are. The consumers being courted are jobbing doctors, and the process is aimed at guessing how these clinicians can be influenced. At the 1990 Paris pharmaceutical conference, Glaxo’s marketing chief told the audience “concepts sell drugs.”²⁰ The academic focus groups are where a company will find out just what concepts are current. After the demise of Vioxx, doctors needed something new for pain relief but rather than sell them Lyrica, a not very good analgesic, Pfizer married Lyrica to fibromyalgia and sold this combination. Fibromyalgia is a suitably vague condition characterized by nonspecific complaints of pain that had been knocking around medicine for a century.²¹

      The new role of medical academics is to broker this process. Where once these academics were the repositories and creators of medical culture, they are now a resource to be plumbed by companies to establish what prescribers can be induced to want rather than what’s best for the patient. The key thing is to establish what prescribers do want from a drug and ensure they appear to get what they want, whether or not there is much basis in the drug to think it might do what the prescriber wants. If pain has become an issue for doctors, the marketing of a new product will emphasize this quality even if there is nothing to recommend the new product for this purpose compared with older products. Companies trumpet the huge research and development budgets needed to bring a drug to market today. But it costs very little to make these medications. Research is undertaken on the new pill, but most of the studies are designed to secure therapeutic niches rather than to advance medical knowledge. The real “research” budget is devoted to establishing the mindset of clinicians at the time of launch. In 2003, it was estimated that thought-leader development in the United States accounted for a stunning 20 percent of marketing costs and was rising,²² compared with 14 percent put into direct-to-consumer ads.²³

      Take the bladder stabilizer Yentreve (duloxetine). Lilly had jettisoned duloxetine as a potential antidepressant in the 1990s because it triggered urinary retention among other effects, but then brought it onto the market in Europe as a bladder stabilizer. When Prozac went off patent in 2001 and its designated successor, Zalutria, appeared to produce cardiac problems, Lilly opted to bring duloxetine back to antidepressant life as Cymbalta. Cymbalta was marketed heavily as a pain reliever in addition to helping depression. Why? Because doctors had told market surveys they often have patients in pain of one sort or another and were uncertain how to treat them.

      Luckily for Lilly, just as Cymbalta was coming to market, the leading painkiller Vioxx was withdrawn from circulation because research showed it caused heart attacks. Anything that would help pain was catapulted forward in the promotions of all companies, and Cymbalta was certainly no exception.²⁴ As a result, a great number of patients attending pain relief clinics or visiting internists or primary care practitioners and complaining of pain were put on it, even though they showed no signs of depression. What doctors were hearing when they listened to the siren song from Cymbalta were their own needs. Duloxetine had nothing to recommend it for pain beyond what other antidepressants have, but Cymbalta relieved doctors’ worries about pain.²⁵ Such marketing might have been developed for Zalutria and simply switched to Cymbalta in just the way that the marketing for one brand of bottled water could be applied to any another. There is nothing in the water that gives substance to any of these perceptions.

      The patient given Cymbalta for pain relief is not to know that it is more likely to lead to agitation, sometimes severe enough to trigger thoughts of suicide—and that the FDA banned its use for urinary incontinence for this very reason. They are not likely to know that Cymbalta is more likely to cause urinary retention than it is to ease pain. But the patient is not the consumer, the doctor is, and his pain is eased by Cymbalta without any side effect to cloud the picture.

      Once the distinguishing feature of a marketing campaign has been identified, the appearances of scientific support are manufactured. A clinical consensus for a drug such as Lyrica (Pfizer’s drug ostensibly to treat fibromyalgia) or Cymbalta for pain, for instance, is built by means of scientific symposia, with articles apparently written by opinion leaders but usually ghostwritten, or by educational initiatives featuring well-known academics.

      Ultimately branding of this sort feeds off blue-skies research and medical education funded by governments in the United States and Europe. Without this there would be very little understanding of the effect a medication has on lipids or bones or blood pressure and as a result very little language available with which to describe the effects of the drugs for marketing purposes. From the point of view of marketing, the advantage of the medical sciences is not that they might lead to better drugs but rather that they provide concepts and languages for marketers to use.

      One of the best examples of this process has been the creation of the notion of chemical imbalance. Neurotransmitters were identified in the brain in the early 1960s. By 1965, this led some to hypothesize that the