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Medicine and the Marketers

When she became pregnant in 2004, 38-year-old Gina Fromm did a range of things that few women would have done in the early 1960s— she took cold rather than hot showers in case she might harm her baby, stopped eating yogurt and incinerated chicken because of the risk of bacterial infection, from listeria to salmonella. She balked at taking prenatal vitamins, though she had been taking Paxil following a fleeting episode of anxiety. She continued to take it through her pregnancy; she had found stopping difficult and her doctor reassured her it posed no risk to her baby. On February 2, 2005, her son was born with congenital heart defects.¹

In the decades following the passage of Senator Kefauver’s bill, women were far less likely to smoke, drink alcohol or coffee, or take painkillers while pregnant. Nevertheless, Paxil and other SSRI antidepressants, among the direct successors of thalidomide, were on their way to becoming the most commonly prescribed drugs in pregnancy— especially in the United States. In 2006, forty-four years after the 1962 amendments to the Food and Drugs Act, the first legal actions were filed for birth defects induced by SSRI antidepressants, resulting in verdicts against GlaxoSmithKline and huge settlements, but this made little dent on the prescribing of SSRIs in pregnancy, which continued to mount.

Nothing about the 1962 amendments obviously predicted the replays of drug-induced birth defects we now have. Medications continued to be available on a prescription-only basis. With the 1962 amendments to the Food and Drugs Act, companies were to be restricted to selling medications for real diseases rather than for trivial indications like halitosis or fleeting anxiety states. Furthermore, from 1962 onward, companies had to demonstrate by means of controlled trials that their remedies did in fact work.

There can be few better symbols of Pharmageddon than prescription only drugs becoming among the most consumed drugs in pregnancy in the face of strengthening warnings that they cause birth defects. The answers to how this could happen lie in great part in how the pharmaceutical companies have managed to capitalize on the very protections put in place by Senator Kefauver in his 1962 bill and in the reforms that defeated him. Prescription-only status has made doctors the targets of a marketing exercise that is far more sophisticated than placing even billions of pages of advertisements in medical journals and bribing doctors to use drugs. As outlined in chapter 1, the patent status of drugs has given companies an incentive to chase blockbuster profits—doing so regardless of patient welfare. Controlled trials have given the companies a means to persuade doctors that snake oil works so well that withholding it in pregnancy would be unethical, and also a means to make problems consequent on treatment vanish. But all of these hinge on the fact that these drugs are available by prescription only.

WHAT THE DOCTOR ORDERED

When Alfred Worcester or Richard Cabot wrote a prescription for a remedy at the dawn of the twentieth century, they were following a centuries-old tradition of asking an apothecary to take certain ingredients and mix them according to a formula (Rx = Recipe). If there was more than one ingredient in the mix, each should have a particular purpose. If the remedy worked, patients were able to take the prescription back to the pharmacy on numerous occasions asking for refills for themselves without further endorsement from the doctor. Alternatively, having once obtained something by prescription that worked, they could revisit the pharmacist and ask for the same medicines again, for family members. A prescription from a doctor was only one means by which people could access the drugs they believed they needed.

Because in Cabot’s day all medicines, including opiates, bromides, barbiturates, chloral hydrate (used for sedation), antiseptics, remedies for the gut, urinary system, and heart and respiratory system were available without recourse to a doctor, the threshold for visiting a doctor was far higher than it is today. Until the middle years of the twentieth century, there was no one being treated for latent diabetes, latent hypertension, or raised lipids. Aside from a few wealthy people engaged in psychoanalysis, no one had contact with the mental health system other than those relatively few who had psychoses and were committed to asylums.

When the US Congress passed the 1906 Food and Drugs Act, it contained no prescription requirement, only a requirement that medicine manufacturers state the contents of the product on the label. The pharmaceutical industry lobbied hard against the act, but once it was in place many enterprising manufacturers found ways of working the new situation to their advantage, for instance, by labeling their product “as approved by the Chemical Bureau.”²

There were no implications here for traditional medical practice. But another regulatory step taken soon thereafter had profound implications. The nineteenth century saw a growing concern about opiate and cocaine abuse, as well as alcoholism. These problems had been of little concern to medicine. Drug addiction, like alcoholism, was considered a social problem, except where the affected people became patients by virtue of cirrhosis or psychosis. After a variety of social approaches to treating the problems of addiction floundered, in 1914 the US Congress passed the Harrison Narcotics Act, which introduced prescription-only status for opiates and cocaine.³ The problem of addiction would be managed, or so it was thought, by making these drugs legally available only through a medical practitioner.

After the contaminated sulfanilamide tragedy of 1937, the 1938 Food, Drugs and Cosmetics Act encouraged a move toward making new drugs available by prescription only. The calculation was that the sulfa drugs were better categorized with insulin and the steroid and thyroid hormones, which were typically if not exclusively administered by doctors. After World War II, in 1951, the prescription-only status for new medicines in the United States was copper-fastened in place with the Humphrey-Durham amendments to the 1938 act, despite vigorous, sustained, and widespread opposition to the move. Critics complained that a system put in place for addicts was inappropriate for free citizens. But by the early 1950s, one of the side effects of having medicines that really worked was becoming clear—drugs that could really benefit, could really harm also. In 1952, Leo Meyler’s Side Effects of Drugs appeared, a first-ever medical compendium of drug-induced injuries.⁴ This new potential for harm took dramatic shape in 1961 with limbless babies born to mothers who had taken thalidomide during pregnancy as a supposedly safer hypnotic than the older barbiturates.⁵

When it came to his hearings in 1959, Senator Kefauver was exercised by the prescription-only status of the new drugs, a unique characteristic found in no other market. As he put it, “He who orders does not buy; and he who buys does not order.” As a consequence, when it came to drugs available by prescription only ordinary consumers could not protect themselves against the monopoly element inherent in trademarks or patents. Patients were critically dependent on their doctors to be uninfluenced by trademarks, patents, or marketing ploys. Doctors had a choice whether to give their patients the latest on-patent and branded drug or perhaps an older, more effective and less expensive drug, but patients had little choice other than to do as prescribed by their doctor.⁶

Thalidomide had been available over the counter in many European countries but exactly the same problems arose in the United States where the premarketing samples were available by prescription only. Indeed the problems may have come to light as quickly as they did because doctors in Germany were not inhibited in recognizing the potential for harm of an over-the-counter drug, as they might have been in the case of a drug essential to their livelihoods. But in the United States in 1962, in the face of the thalidomide disaster, retaining the prescription-only status of drugs seemed to make sense: doctors retained some patina of skepticism about drug claims due to medicine’s long-standing opposition to quackery, and doctors appeared to be the people who would be able to quarry information from drug companies about possible adverse side effects of their products.

Before 1962 prescription-only status was still something of a novelty—after 1962 it became the center of the distribution system for new drugs when companies were required not only to make their drugs available only through doctors but also to prove that their drugs worked for some medical condition in order to get FDA approval. This combination of controls must have looked pretty foolproof in 1962, but it has not turned out to be an effective way to constrain the pharmaceutical industry within a medical framework. Quite the reverse. When a pharmaceutical company gets a drug on the market for lowering cholesterol, for osteoporosis, or for erectile dysfunction, this now marks the point at which the company begins to sell the condition, the point at which they can gear up to reengineer the medical marketplace to suit their product, as Abbott did with bipolar disorder to make it Depakote-friendly. It seems extraordinary now that no one in 1962 seems to have realized that if pharmaceutical companies were restricted to marketing drugs for diseases, they might start to market diseases.

Had pharmaceutical companies not been required to demonstrate a drug’s efficacy in treating a particular disorder, we might all have ended up with a lot fewer diseases recorded in our medical records. The first antidepressants would have been marketed as tonics or stimulants. To get St. John’s wort, an herb with SSRI properties, we just have to feel stressed and buy it over the counter where it is sold as a tonic, but to get Prozac now, we have to be officially diagnosed as depressed. In a similar fashion, the statins might have been marketed on the promise of restoring inner youthfulness, or getting our arteries in shape, rather than for a supposed cholesterol disorder, or the biphosphonates might have been aimed at restoring youthful bones rather than for osteoporosis. As insurance companies reimburse in response to diagnoses, fewer diagnoses would likely have reduced our need for doctors in addition to reducing the number of diseases.

The third medical requirement of the 1962 amendments was that companies demonstrate their products worked in well-controlled clinical trials. This was smuggled into the final bill through the efforts of Louis Lasagna, a professor of pharmacology and a believer in controlled trials, who was attempting at the time to encourage some use of controlled trials, rather than trying to make them mandatory.⁷ Lasagna himself had undertaken the only controlled trial of thalidomide ever done, through which it sailed—an effective hypnotic free of significant side effects.

The copper-fastening of prescription-only arrangements that came out of the Kefauver hearings would alone have put doctors in the sights of pharmaceutical company marketing departments in a way they had never been before. But constraining companies to market their drugs for diseases and to demonstrate their efficacy through what was then a new medical invention, the controlled trial, made it necessary for companies not just to have doctors in their sights but to understand doctors better than doctors understood themselves.

In the case of some hugely profitable trademarked drugs, such as Marlboro, medicine has played an honorable part in bringing lethal problems to light. But what would have happened had tobacco been available by prescription only? It is clearly helpful for ulcerative colitis. In all probability it could be shown to be just as good an antidepressant as Prozac and the SSRIs—so the market might have been substantial. How quick then would doctors have been to do the independent studies that pinpointed the problems linked to smoking or to insist on the seriousness of the risks while the tobacco industry was systematically creating doubt about those risks?

Doctors don’t view themselves as consumers, subject not only to the extraordinary pressures that modern marketing can bring to bear on any consumer but also, by virtue of prescription-only arrangements, to these forces in the most concentrated form that exists anywhere on the globe. Typically, they blithely go their way without seeing the need to understand marketing. They bunker down behind a Maginot Line of what they believe are untainted controlled trials and evidence-based medicine, unaware that the tank divisions and air force of their opponents give daily thanks for that Maginot Line.

THE RISE OF THE BLOCKBUSTER

The possibilities for a new generation of branded medicines—and extraordinary sales—that opened up on the back of a regime that allowed drugs to be patented and that made these drugs available on a prescription-only basis were first revealed in the course of a battle in the 1980s between pharmaceutical giants Glaxo and SmithKline over the ulcer drugs Tagamet (cimetidine) and Zantac (ranitidine).

James Black was one of the most successful medicinal chemists ever; he was also one of the first to win a Nobel Prize while working in the pharmaceutical industry. Black had initially worked for Imperial Chemical Industries, where he had developed the concept of a beta-blocker. These drugs, which blocked the beta-adrenergic receptors on which stress hormones like epinephrine exert their effects throughout the body, turned out to be particularly useful for treating hypertension, the most rapidly growing medical market in the 1970s.

Black then moved to SmithKline, where he turned his attention to the antihistamines, helping to distinguish among two different histamine receptors, H-1 and H-2. This opened the way to develop H-2 blockers that would target histamine receptors in the gut, reducing gastric acid production, then thought to be responsible for ulcers. Tagamet was the result, a drug that embodied a genuinely novel approach to the treatment of duodenal ulcers, then one of biggest problems in internal medicine.⁸ Within a few years of its introduction, surgery for ulcers had become a rarity—had Tagamet been available earlier, it would have saved my mother much misery. This epitomized the best hopes of both science and industry—new and innovative products making it into healthcare and making a big difference to patients.

In the course of developing Tagamet, Black presented details of his experiments at scientific meetings, stimulating interest among chemists at Glaxo, who also determined to develop an H-2 blocker. Glaxo’s efforts led to Zantac, a drug almost identical to Tagamet. Since Tagamet had been the breakthrough compound and had come on the market in 1979, six years before Zantac, and with the prestige of Black’s endorsement, few doubted that Tagament’s sales would vastly outstrip those of Zantac.

Glaxo, far from undercutting the price of Tagamet, as might have been expected in a normal market, decided to make Zantac pricier. And it put huge resources into marketing, which focused on minor differences in the side-effect profiles of the two drugs. Much to the surprise of observers, Zantac’s revenues soon outstripped Tagamet’s, and it became the first blockbuster—a drug that makes at least a billion dollars per year.⁹

Glaxo and SmithKline merged at the turn of the millennium to become the biggest pharmaceutical company in the world. But before they did, Glaxo’s response to an exciting development in the science of ulcers is indicative of important shifts that were taking place in the world of medicine and corporate interest. In Australia, Barry Marshall, then a medical resident in Perth, spotted an unusual bacterium, helicobacter pylori, in tissues removed from ulcers. This led him to a series of experiments where he cultured helicobacter, drank it, produced an ulcer, and later cured his own ulcer with antibiotics.¹⁰

Marshall made overtures to Glaxo but found they had no interest in a cure for ulcers. The beauty of H-2 blockers was that once they began taking them, many patients remained on them indefinitely. Actually eliminating ulcers, the treatment of which had just become the cash cow of the pharmaceutical industry, was not what Glaxo had in mind. The decade between the contrasting scientific experiments of James Black and Barry Marshall had propelled medicine into a new world, one in which it could not be assumed that science and business were on the same side, as they had appeared to have been over the previous three decades.

Zantac was a brand like no other. It came with attention to color coding, with free pens and trinkets for doctors, and a lot of support for doctors to attend educational meetings nationally and internationally. It set a template for aggressive drug promotion. Its very success led, in reaction, to movements like No Free Lunch, a group set up by Bob Goodman to persuade doctors to remain independent of pharmaceutical companies by refusing the free pens, lunches, and the like that companies handed out so liberally. Glaxo’s aggressive marketing at the end of the 1980s also made many doctors more receptive to the idea that evidence-based medicine, which emerged in the 1990s, could be used as a way to contain the power of marketing.

But No Free Lunch and similar efforts to eliminate conflicts of interest fail to ask just what it is that would make a brand appealing to doctors. A brand is something whose value lies in the perception of the beholder—and in this case doctors repeatedly tell us that the evidence about a drug’s benefits and risks trumps the color coding of the capsule or the lunches, no matter how good they might be. And insofar as creating a brand involves building a set of exclusively positive associations and eliminating any negative associations, this is not going to be done by getting the color right.

The problem is that a brand is meant to be an uncomplicated good. It is a partial truth that seduces by directing our attention away from any messier realities. It doesn’t fart; it doesn’t have body odor. Against a background of clinical complexity it offers a point of reassurance. But it is, by this definition, incompatible with a medicine, which is—or was—understood to be a poison whose delivery involves a judicious balancing of risks and benefits.

The combination of brands like this and prescription-only privileges leads to a tragedy in the classic sense of that word—as with Hamlet, “whose virtues else be they as pure as grace as infinite as man may undergo, shall in the general censure take corruption from the particular fault.” Here’s how. Brands married to product patents have created the conditions that have made blockbusters possible, and the fortunes of pharmaceutical companies increasingly now depend on the success of these blockbusters and their branding. They have to be hyped to the max and their hazards concealed. These dynamics of brand creation are, through prescription-only status, welded to an profound bias in medicine—doctors tend to attribute any benefits in a patient’s state to what they have done and couple this with a tendency to overlook any harm they might have done. Doctors have to be enthusiastic about treatment—their very enthusiasm can make the difference between success and failure. Being readily able also to spot the harms they do would likely in many cases lead to clinical paralysis.

The fortunes of pharmaceutical companies hinge on this weld holding fast. The tragedy is that there is little risk of it coming undone: both companies and clinicians are biased to attribute any harms to the disease being treated—it is depression that gives rise to suicidality in patients on antidepressants, not the drugs; it is the poor state of a person’s arteries that leads to coronary artery bypass surgery and is responsible for any confusion after the surgery rather than anything that happened on the operating table; it is schizophrenia that gives rise to a disfiguring neurological condition, tardive dyskinesia, rather than treatment with anti- psychotics. For thirty years the outcomes for lung cancer have remained almost unchanged. Millions of people have died during this period, after having radical surgery, intense radiotherapy, or intense chemotherapy. If these treatments extended the life of some yet overall life expectancy remained the same, there must also be an equal number whose lives were shortened by treatment, but you will hunt high and low to find any whose deaths are attributed to the treatment rather than the disease.

When it comes to the harms following ingestion of over-the-counter or illegal drugs, from the end of the nineteenth century the medical profession had no difficulty seeing their problems and expressing opinions through bodies such as the AMA. But once the drugs are made available by prescription only through the clinician, there is no independent voice of any standing to urge caution. Against this clinical background, the dynamics of branding produce something close to a pure toxin for medical care.

The contrasting fates of reserpine and Prozac bring this out. In the early 1950s, reserpine, one of the first antihypertensives and first tranquilizers, was linked to suicide induction. Owing to the differing patent regimes at the time, twenty-six different companies produced reserpine and so no one manufacturer could have made it into a proprietary blockbuster. Therefore no company had an incentive to defend it to the death, and as a result while many doctors refused to concede a treatment they gave might have caused a problem, the views of others could be heard. A link between reserpine and agitation was established and reserpine fell into disfavor.

But in 1990, when similar concerns erupted that Prozac could trigger suicides, the situation was quite different. There was and could be only one Prozac, and Lilly had all their eggs in the Prozac basket. They could not readily admit their brand might have a flaw. As Leigh Thompson, Lilly’s chief scientific officer put it in an internal e-mail that later came to light in a court case:

I am concerned about reports I get re UK attitude toward Prozac safety. Leber (FDA) suggested a few minutes ago we use CSM database to compare Prozac aggression and suicidal ideation with other antidepressants in UK. Although he is a fan of Prozac and believes a lot of this is garbage, he is clearly a political creature and will have to respond to pressures. I hope Patrick realizes that Lilly can go down the tubes if we lose Prozac and just one event in the UK can cost us that.¹¹

Several years later company documents for Lilly’s post-Prozac blockbuster Zyprexa made it clear that

The company is betting the farm on Zyprexa. The ability of Eli Lilly to remain independent and emerge as the fastest growing pharma company of the decade depends solely on our ability to achieve world class commercialization of Zyprexa.¹²

Prozac, Zyprexa, and other such blockbusters are products that come with a life plan that covers their use in all global markets.¹³ Even before the launch of potential blockbusters, ways of promoting their use in children and the elderly, without undertaking clinical trials to demonstrate efficacy or safety, is envisaged. The necessity of acknowledging a side effect that might restrict this use is not part of the plan. When a company is faced with defending a brand that is essential to its survival, commercial logic dictates that it will take any steps necessary to preempt the emergence of a hazard, including doctoring the evidence. This commercial logic led to a relentless marketing of Zyprexa that ultimately saw it being given to children as young as twelve months of age, its clinician prescribers seemingly unable to see the massive weight gain it produces, the diabetes it triggers, the raised lipids it leads to, and the premature deaths it causes.¹⁴

As the story of H-2 blockers and the treatment of ulcers suggests, drug companies have little interest in innovative treatments that would eradicate a condition for which they have on-patent drugs that manage it after some fashion. When ulcers vanished, after the introduction of antibiotics, companies like Astra-Zeneca with a new generation of gastric acid antagonists, such as Prilosec, turned to GERD (gastro esophageal reflux disease) to replace it. This disease, which now seems so widespread and crippling, was infrequently encountered when I was training, and as such it is difficult to believe it doesn’t stem at least in part from our increasingly unbalanced and artificial diets and lifestyles. While there are unquestionably severe cases that need urgent medical treatment, it also seems the case that a large number of digestive discomforts that might be better handled by changing lifestyles have now been medicalized and are managed with medication.

Quite extraordinarily GERD has even spread into infancy, incorporating colic, a disorder that lasts a few months and responds to care in the real sense. The first drug treatment for GERD in infants—Prepulsid (cisapride)—killed significant numbers of children where colic had never been known to kill children before.¹⁵ The shock of Prepulsid-induced deaths did not lead to a return to traditional medical care of colic— children instead are now getting Prilosec (omeprazole) and other successors of Zantac.

At the eighteenth annual Pharmaceutical Conference in Paris in June 1990, Christopher Adam, then the head of marketing at Glaxo told the meeting “we are moving into the mega-product age.”¹⁶ Right he was. Zantac had just become the first blockbuster. The next year all blockbusters combined only comprised 6 percent of the market, but by 1997, when SSRIs like Prozac were the darlings of the media, this had grown to 18 percent, and by 2001 to 45 percent, under the impact of Lipitor and the statins.¹⁷ There is no blockbuster that is a life-saving drug. They are all lifestyle or risk management drugs.

In 1990, market analysts perceived two threats to Glaxo’s position as the largest drug company in the world—the possible expiry of its patent on Zantac and the emergence of Prilosec, a new drug for ulcers. In fact the danger came from Barry Marshall’s research. Prilosec did displace Zantac but for the GERD rather than the ulcer market, forcing Glaxo into a series of mergers in order to sustain its position among the leading companies. In 1995, it merged with Burroughs Wellcome, at which time its chief executive, Richard Sykes, made it clear he still regarded the company as a serious research company that would have nothing to do with lifestyle drugs like Prozac. Five years later it merged with SmithKline Beecham, whose fortunes rode on Paxil, the company’s biggest earner since. By this time Sykes was gone. The market was changing the character of drug companies and in turn the shape of medicine.

THE FACE IN THE MIRROR

The idea that brands such as Lipitor, Paxil, and Fosamax might now have penetrated medical practice in a way that brands like Clark Stanley’s Snake Oil or Beecham’s Pills never did and that these modern brands might now play as big a part in medicine as Nike and Reebok do for running shoes and Lexus and BMW do for cars is not an idea that sits comfortably with the medical profession’s idea of itself.

In the world of medicine most doctors come from, drugs are good, though they are unfortunately sold by slick if rather sleazy salespeople to whom doctors might try to be polite but whom they otherwise try to avoid—unless “these people” are picking up the drinks tab. But in the new world of medicine, the person doing the selling is not the sleazy- looking suit standing by the exhibit. That person is there to distract attention from the fact that one by one doctors are having marketed back to them exactly what they say are the things that count for them. The industry needs a person out there whom the doctor can identify as a source of corruption, someone they can resist, the way they might resist an obvious honeypot. In this new world, if a group like No Free Lunch didn’t exist, the pharmaceutical industry would have to invent it.

In other industries, when companies manufacture a product they have to move it from factory to retail outlets where it competes with other products and they have to generate demand among consumers. The ideal arrangement is to have a dedicated showroom, such as automobile makers and Apple do, where purchases become almost inevitable as there are no competing brands in sight and, in the case of cars, nothing praising the virtues of walking, running, cycling, or any other means of transport. In the case of a branded drug, the task is to get on a hospital’s or managed care company’s list of approved drugs as well as into national guidelines and to have key articles placed in all the prominent journals. We shall see in chapters 4 and 5 how companies manage this and manage to eliminate competing influences, so that when the doctor gets to the point of purchase, the purchase is as inevitable as it is in a car showroom, 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 amounts of one or another of two common neurotransmitters, norepinephrine and serotonin, are lowered in depression and that antidepressants could top them up. By 1970, psychopharmacologists had abandoned these hypotheses because of clear inadequacy.²⁶ But twenty years later, the idea that serotonin was low in depression and restored to normal by treatment was resurrected within the marketing departments of SmithKline Beecham, Lilly, and Pfizer, as part of the sales pitch for Paxil, Prozac, and Zoloft. It was marketing copy par excellence, too tempting to spurn. In fact, mindless patter about restoring chemical balances did a great deal to make the SSRIs among the most profitable income streams for the pharmaceutical industry from 1990 onward. In similar fashion when selling drugs for osteoporosis, cholesterol reduction, asthma, and other conditions, marketers cherry- pick from the language of the appropriate science to dress up their products. As they put it themselves, they leverage the bits of the science base that suit them.

In addition to using information from the basic sciences, one of the clearest strategies companies use is to market diseases in the expectation that sales of the pills promoted for them will follow. This has happened from the 1950s onward, when Merck educated physicians to recognize raised blood pressure (hypertension) and its consequences after their new diuretic agent, Diuril, turned out to have antihypertensive properties. They convened symposia and sponsored studies on the benefits of monitoring hypertension.²⁷ This approach speaks directly to clinicians in clinical language. It also puts an ethical onus on them to eliminate a disease by prescribing a pill—one that comes sanctioned by the experts in the field.

Patients also have to be softened up so they are receptive to the idea of being prescribed a statin, or an antihypertensive, or a biphosphonate for their bones. In the United States direct-to-consumer advertisements school people on the importance of their “figures”—their lipid levels, blood pressure, and bone densities—or alert them to the possibility that what they regard as restless legs may be in fact be an illness,²⁸ or that feelings of urgency as regards micturition, low grade pain, or less than perfect sexual potency may be illnesses that can be treated. Ask your doctor if…

Elsewhere in the world promotional stories appearing in the health pages of newspapers and magazines fulfill the same function. PR firms place stories in the media and help sponsor books such as Listening to Prozac,29 while marketers increasingly utilize Internet sites where patients can diagnose themselves and take the resulting information back to their doctors. If there is a buzz around some disorder the British, Australian, or French media are naturally going to be interested to feature it, even though direct-to-consumer ads are not permitted in these countries. They may portray the condition as one that may be as effectively treated without medication, or indeed the program may come out vigorously against regarding certain states as disorders in need of treatment, but simply raising consciousness about the condition is taken advantage of by clever drug marketers. The company touch is subtle—sponsored symposia, for instance, will regularly feature talks by academics advocating nondrug approaches to an illness. These talks fill the same role as the comic at a burlesque show—a straight man is needed at intervals between the disrobing women.³⁰

Capturing understanding is the prelude to selling pills. The marketer aims to convert people from thinking that childhood has its vicissitudes and developmental stages and that most distress and abnormalities are transient to thinking in terms of diseases and chemical imbalances that cry out for treatment, from depression to ADHD, autism to juvenile bipolar disorder. The normal elevations of blood lipids and thinning of bones that go with age are transformed into diseases—moreover, diseases that have become as much commodities as are iPods and as subject to fashion, with the main determinant of the fashion cycle being the patent life of a drug.

So successful have the marketers been that it is now common practice among them to assume that few if any doctors will have any medical thoughts in their mind other than what is put there by either their own company or one of their competitors. They find even fewer physicians aware of how they are being sold pills, much less able to put up a challenge. Even if there were a challenge, just as Che Guevara has ended up as an establishment logo, so also can many forms of protest be incorporated by the marketers’ machinery.³¹ Just as a hostile review can sell books, companies have even learned how to increase sales in the face of FDA requirements to issue warnings about hazards such as birth defects due to Paxil, by “controversializing” the issues.

BRAND NEW MEDICINE

When asked to comment on the significance of the French Revolution, Mao Tse-tung and Chou En-lai are reputed to have said it was still too soon to judge. Two hundred years ago, in the midst of that revolution, Western medicine took on much of its modern character. In addition to the traditional and private relationship between doctor and patient, a new duty to look after the health of the wider population emerged, setting up new relationships between doctors and their patients and the state. One of the key players in shaping the new medicine was Philippe Pinel, among the most prominent of a new breed of doctors who stood in contrast to the society doctors of the eighteenth and nineteenth centuries that made a living treating wealthy patients with hypochondriacal ailments.³²

Faced with the competing pressures on doctors, Pinel stressed that physicians needed to combine their roles as givers of care and as scientists. It was only through the application of science, he said, that doctors would be able to distinguish among the conditions they were treating and establish the natural history of each. This would give them the best chance to discover the anatomical basis of these conditions and might lead to new therapies for both individual patients and the wider community.

Pinel’s approach both to science and its public dimension was vindicated in the 1880s, when laboratory science began to demonstrate links between diseases and microbes. Once it was clear infections were transmissible, medicine had to have a public dimension. In our day this dimension is global. Drug-resistant tuberculosis in Russia and AIDS in Africa pose threats to all of us.³³

If in principle the mission of medicine has been to treat the diseased and dying wherever they are, that of the pharmaceutical industry has increasingly been to protect its patents and its profits. The clash of these values came to a dramatic head in the late 1990s with the struggles to make antiretroviral drugs available in sub-Saharan Africa for the treatment of HIV-AIDS, just as Glaxo Wellcome and SmithKline Beecham were in merger talks. The first of the antiretroviral drugs, zidovudine, also called AZT, was developed in university laboratories with public funding—the first of which, for marketing and distribution purposes, was offered to Burroughs Wellcome (prior to the merger with Glaxo) to patent, which it did and then marketed as Retrovir.³⁴ The fear of AIDS in the 1990s ensured that Glaxo Wellcome and other companies marketing these drugs had a rich return on these products.

In the early 1980s AIDS appeared to be confined to the United States or the Western Hemisphere, but by the 1990s it was clear that there were far higher rates of infection in Africa and a risk of the disorder spreading to Asia and elsewhere. The rates were so high that many African countries faced being crippled by the disease. Supported by all other companies, GlaxoSmithKline (GSK) refused to either permit other companies to offer the drug in generic form at much lower prices or to lower the price on AZT themselves to a level that would make it possible for the hundreds of thousands suffering in Africa to benefit from it and thereby stem the tide of an enormous tragedy. To do so, GSK argued, would breach patent law in a manner that would compromise future drug discoveries. It was as though the companies who produced diphtheria antitoxin a century earlier had refused to make it available. The outrage of almost the entire world forced GSK to back down.

Glaxo and other pharmaceutical companies have been willing to treat the West and, more recently, the wealthy parts of China, India, and Brazil, as gated communities, within which one form of healthcare will be available and outside of which no questions will be asked. Some of those inside the gates may regret this policy, but provided their children and families are not the ones dying from diphtheria or AIDS these regrets are unlikely to lead to action. But this is short-sighted in the extreme. The same patent and marketing factors that have led companies to lose interest in developing drugs for Third World diseases if these do not afford a sufficient return on investment by today’s blockbuster standards, mean that the drug companies are no longer likely to play the kind of role they once did in eliminating disorders like diphtheria or bacterial endocarditis. Indeed, they didn’t develop AZT or the other retrovirals for AIDS; these applications were developed elsewhere with public funds. They are not likely to develop better anticonvulsants for epilepsy or bring treatments for multiple sclerosis on the market, since even within the gated communities of the developed world the incidence of these conditions is such that it is not worth their while to make the investment. Return on investment rather than elimination of disease is, after all, what drives a pharmaceutical company.

This philosophy is as diametrically opposed to that of Philippe Pinel, Alfred Worcester, and Richard Cabot as it is possible to get. For over a century patients have assumed that the knowledge a doctor like Cabot brings to helping them stems primarily from what is known about the condition being treated or that what a doctor like Worcester brings stems from a judicious appraisal of the limits of current knowledge and treatments. But in the past two decades what is “known” has come increasingly to be dominated by the self-interested constructions of the pharmaceutical companies, through the activities they sponsor, the kind of research they promote, and the information they choose to reveal—or conceal. Under siege, doctors like Dr. N have turned to the appearances of science and spend their time filling standardized forms in medication clinics rather than talking to or looking at their patients. In this process they have become the faithful if unwitting collaborators of the pharmaceutical companies, almost as though the debates between Cabot and Worcester about the purpose of medicine had not taken place a century ago—or worse, almost as though Clark Stanley marketing snake oil or Thomas Beecham marketing his pills had not faded away in the face of developments in medical science or a growing commitment to medical care of the type Pinel and Worcester advocated but had instead taken over the health service business.

In 1909 Beecham’s Pills ran into trouble when their claims to be a cure-all for lifestyle problems included suggestions that this combination of aloes, ginger, and soap, whose retail price was 500 percent of its costs of production, might be useful for “maladies of indiscretion.”³⁵ This claim was read as offering a “morning after” service. In 2009, GSK, whose fortunes at the time of the patent disputes over AZT rested on the SSRI Paxil, a drug a former CEO had derided as a lifestyle drug but which Glaxo had inherited when taking over SmithKline Beecham, lost a legal verdict to Michelle David, who claimed Paxil had caused congenital heart defects in her son Lyam Kilker.³⁶ The evidence in this, and Gina Fromm’s subsequent case, made it clear that in addition to doubling rates of congenital malformations it doubles the rate of miscarriages and increases voluntary terminations of pregnancy.

Yet extraordinarily in the face of this evidence not only doctors but even ethicists line up to say antidepressants are being underused in pregnancy.³⁷ There is a suspension of common sense here that has been brought about by company marketing of controlled trials and evidence based medicine. Ironically a requirement for controlled trials was built into Senator Kefauver’s 1962 amendments as this seemed a method to limit rather than promote treatments, but these trials have in fact become the primary marketing tool of pharmaceutical companies. The marketers have selected the trials that suit, had them polished by ghostwriters just as much as a political speech might be, before smuggling them past the peer review systems of academic journals and meetings. But none of this would have the power to influence doctors had the very meaning of clinical trials not been turned inside out.