The Body Hunters (10 page)

The abundance of statins stood in direct contrast to their slender benefits, especially for the millions of Americans who weren't at especially high risk for heart disease. According to one analysis, more than four hundred people with mild cholesterol would need to be treated with statin drugs in order to prevent a single coronary heart disease event,
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a success rate that pales in comparison to improved diet and exercise regimes. After all, half of all heart attacks occur in people who have normal cholesterol levels.
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Statin makers were forced to exaggerate, with all the problematic public health effects that would follow: “You may think you're healthy,” Pfizer ads warned, over tragic scenes of middle-aged men dramatically collapsing midmeal, “but too much cholesterol in your blood can cause a heart attack.”
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With all the competition in the already crowded field AstraZeneca lavished a $1 billion advertising budget on Crestor.
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One way drug companies could distinguish their otherwise indistinguishable me-too drugs was by tinkering with the dose. At lower doses the prescription antihistamines effected more marketable claims—they were less sedating, albeit also, it seemed, less effective. In fact, in the RCTs of Claritin submitted for FDA approval, the drug appeared only marginally better than nothing at all: in one trial Claritin affected a 46 percent improvement compared to 35 percent on placebo. According to an allergist on the FDA advisory committee that considered the drug, at the dose that Schering wanted to sell it, Claritin “is not very different than placebo clinically.” A larger dose might be more effective but would make patients drowsy, undermining the one marketing claim that set the drug apart from its much cheaper over-the-counter alternatives. Schering wasn't interested.
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In statin drugs higher doses led to better marketing claims. At higher doses statins could reduce cholesterol levels more rapidly and severely, allowing drugmakers to claim their statins were “more effective” and “easier to prescribe” than alternative statins. The trouble, critics complained, was that the higher and one-size-fits-all doses added diminishingly little more effectiveness while significantly increasing the risk of
adverse events, such as rhabdomyolysis (the potentially fatal breakdown of muscle fibers).
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All of the statin drugs cause rhabdomyolysis to some degree, a factoid that generally emerged after the drugs hit pharmacy shelves. The problem was so bad with Bayer's statin Baycol—based on the number of deaths reported, it appears that over six hundred people may have been killed by the drug
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—that it was withdrawn after a few years on the market. The latest competitor, AstraZeneca's Crestor (launched in 2004), is being sold at an even higher dose than the other statins, and triggered cases of rhabdomyolysis even before the FDA approved it.
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While consumers replaced doctors as the originating sources for new drug prescriptions, physicians' ability to judge new drugs independently weakened. The pressure on doctors to liberally dole out prescriptions for the new blockbuster drugs is intense. Drug company dollars have penetrated nearly every corner of medicine, from medical school to hospital corridors and continuing medical education courses, where they bombard physicians with positive information about new drugs, free samples, and luxurious perks for the biggest prescribers.

Exposés of doctors accepting elaborate resort vacations and free concert tickets from drug companies grab headlines, but the more run-of-the-mill drug marketing, in which boosterism masquerades as research and education, typically goes unreported. For example, nine out of ten physicians rely on the
Physicians' Desk Reference
for information about which drugs to prescribe.
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The
PDR
, delivered free of charge to all practicing physicians in the country and updated annually, presents itself as a useful, unbiased reference book. In fact, the
PDR
is funded by drug companies, and the book itself is simply an alphabetical compendium of drug companies' product labels.
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If research not funded by the industry reveals that a drug is ineffective, dangerous, or redundant, doctors who rely on the
PDR
would never know it, as such information is excluded from the
PDR
(unless the FDA orders a
label change). Nor are independent drug reference books able to compete against the
PDR
. The well-regarded
AMA Drug Evaluations
, for example, sputtered along on less than twenty thousand copies worth of sales every year before admitting defeat and ceasing publication in 1996.
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In many states medical boards themselves encourage doctors to participate in drug company–sponsored seminars and workshops. Thirty-four states require that doctors participate in continuing medical education (CME) programs every year in order to maintain their licenses to practice. More than half of the cost of these programs are now paid by drug companies. Their intent is not to teach doctors about the pros and cons of new drug therapies, or to advocate nondrug solutions to medical problems. They are instead openly regarded as marketing opportunities. “Medical education is a powerful tool that can deliver your message,” one CME company announced to drug companies.
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Industry-sponsored CME programs work, too: one study, comparing outcomes among heart attack patients in states with CME requirements and those without found little difference between the two—save for the fact that patients in CME states were “significantly more likely to receive brands of thrombolytic . . . drugs manufactured by drug companies that often sponsor CME events,” as
Heart Disease Weekly
reported in 2004.
¹⁰⁴

If all that wasn't sufficient, drug companies often resort to simply paying doctors to prescribe their drugs. Thousands of practicing physicians are enticed into switching their patients to new drugs through industry-sponsored postmarketing “trials.” For these putative trials companies find physicians who are most likely to prescribe their new drug, and pay them hundreds or even thousands of dollars for “enrolling” patients in the “study” of the new drug. The idea is to entice doctors and patients into trying a new drug in the hope that they'll continue the prescription after the trial ends, this time at top dollar. “Make no mistake about it,” announced one industry marketing memo. “The . . . study is the single most important sales initiative. . . . [I]f at least
20,000 of the 25,000 patients involved in the study remain on [the drug], it could mean up to a $10,000,000 boost in sales.”
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As doctors' prestige and salaries nosedive under managed care, drug companies lavish them with free vacations, dinners, reference books, and drug samples. The billions spent on direct-to-consumer marketing had patients asking for drugs by name. Was it really surprising then, that when Americans visited their doctors, two out or three times they'd come home with a new prescription or a free drug sample?
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As each check and balance on the drug industry—rigorous regulation, fairly informed consumers, skeptical physicians—fell by the wayside, so too did the independence of academic medical researchers, who could easily destroy the marketing goliath that the blockbuster drug industry has become. Just as a
60 Minutes
exposé or a scathing
Consumer Reports
review could destroy the sales of other dubious products, a single study exposing the overblown claims of drug marketers, published in a prestigious medical journal like the
New England Journal of Medicine
or
JAMA
, could devastate a new drug.

Fortunately for the industry, though, by the mid-1990s the handful of independent medical researchers who investigated the veracity of drug industry marketing claims were “an endangered species facing extinction,” according to the NIH. Enchanted by the dazzling promise of the new genetics revolution—so-called basic research based in laboratories—NIH funding for the messy work of experimenting on humans had dried up, dropping to just one-tenth of the NIH's extramural budget.
¹⁰⁷

It was either take drug company money or perish, many academic researchers felt. The drug industry, by 1995, was spending nearly 40 percent more than the government did on medical research.
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“For academic medicine not to avail itself of the resources of the pharmaceutical industry and private sector would be foolish,” said University of North Carolina psychiatry professor Jeffrey
Lieberman to the
Wall Street Journal
. “It would be like major sports saying they won't take advertising from Nike.”
¹⁰⁹

And so, academic medical researchers under industry contracts cranked out a steady stream of positive research detailing minor differences between nearly identical drugs. According to one analysis, 95 percent of industry-sponsored studies of cancer drugs rendered favorable results as opposed to just 62 percent of those funded by nonprofits. “Is academic medicine for sale?” wondered the
New England Journal of Medicine
's then editor Marcia Angell in a May 2000 editorial.
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“No,” came the response from one cynic. “The current owner is very happy with it.”
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Drug companies retorted that they conducted the exacting randomized controlled trials that the FDA's regulations required. The model's integrity is unassailable, no matter who implements it, they argued. Experts in the field, by and large, agreed.
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And yet, there is wiggle room in RCTs. They are ill equipped to find answers to questions they don't ask. What's more, they can be subtly manipulated to make new drugs look better than they are. A new drug might be pitted against a lower dose of its competitor drug, or against an inferior form of it. The majority of trials comparing Pfizer's fluconazole to amphotericin B, for example, administered the amphotericin orally, even though that drug works better intravenously. Or new drugs might be tested in subjects much heartier than those who would end up swallowing the meds later on, lessening side effects. For example, arthritis-drug makers fill over 97 percent of the spots in their trials with subjects under sixty-five years of age, despite the fact that most of the patients who will be prescribed the drugs are elderly.
¹¹³

Despite such hijinks, occasionally industry-sponsored academics come up with results that don't jibe with a company's marketing message. By and large such studies are squelched and the academics sacked. A few months of data might be dropped, for example, or a study might be redesigned to render a more pleasing result. Academics who don't go along with the game risk being
slapped with lawsuits. “Companies can play hardball,” complained Wake Forest University public health professor Curt Furberg, MD. “Many investigators can't play hardball back.”
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Bruce Psaty, one the nation's leading cardiovascular researchers, saw firsthand just how.
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During the 1990s Psaty undertook a study funded by the National Heart, Blood, and Lung Institute, looking into the differences between patients who took various popular calcium channel blocker drugs for their high blood pressure and those who didn't. At the time around six million Americans were prescribed calcium channel blockers, but few long-term studies had been conducted on their safety.
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This was precisely the kind of research that the drug industry would be loath to take on: a study that pitted rival drugs in a head-to-head comparison. And Psaty's findings were exactly the kind of results that drug companies would be loath to hear. According to his study, contrary to drugmakers' marketing messages, the most popular drugs increased the risk of a heart attack by about 60 percent (from 10 in 1,000 to 16 in 1,000).
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With millions of people taking the heavily marketed drugs, the increased risk was a significant public health concern.

The results were quickly picked up by the Associated Press and other media outlets. Panic ensued. Hundreds of calls from distraught patients, doctors, and drug companies poured in to Psaty's office, forcing him to hire extra help. Doctors and industry execs were irate, calling Psaty's report alarmist. “This is a great example of news that's not ready for prime time,” seethed the American Heart Association's Rodman Starke.
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While
Pharmaceutical Executive
magazine pooh-poohed Psaty's findings—“many people who die are taking some drugs,” the magazine noted breezily
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—Pfizer demanded that Psaty's university submit mountains of notes, meeting minutes, and records for their review. Drug maufacturers criticized Psaty's study and, he says, publicly questioned his integrity. The embattled Psaty and other similarly harassed researchers aired their sad story in a
1997
New England Journal of Medicine
paper, under the headline “The messenger under attack.”
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By 2000, the proportion of the nation's health care budget devoted to drugs was growing by 15 percent every year—almost twice the rate of growth in spending for hospitals and doctors—and was expected to continue to rise over the coming decade.
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While the industry takes pains to point out how this outlay of cash actually saves society money, by preventing costly hospitalizations, in fact most of the increased spending on drugs centered around just a handful of heavily marketed, brand-name drugs—not much more than two dozen of the over nine thousand drugs on the market. The bestsellers included such nakedly commercial hits as Astra-Zeneca's acid-reflux drug Nexium, which contains the same active molecule as the off-patent drug that preceded it, Prilosec, and allergy drug Clarinex, the metabolite of its off-patent parent drug Claritin.
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