The Body Hunters (9 page)

Since then, numerous studies have exposed the hollow center of surrogate markers: drugs that lower cholesterol can increase mortality; drugs that reduce blood pressure increase patients' risk of heart attacks; AIDS drugs that increase CD4 counts have no effect on the course of the disease; and drugs that reduce tumors don't extend lives. And yet drugs that have proven they can do little more than alter these ghostly proxies continue to be approved by the FDA.
⁵⁵

Then, in 1992, with the passage of the Prescription Drug User's Fee Act FDA reviewers who painstakingly analyzed data on new drugs to ensure their safety were burdened with punishing deadlines. Under the new law drug companies would pay the FDA directly—up to $672,000 for each new drug application in 2005—in exchange for speedier deliberation times.
⁵⁶
Regardless of the complexity of the drug or its safety profile, the FDA would be bound to meet strict new deadlines, shaving off weeks from review times and making the agency feel, as some insiders said,
like a sweatshop.
⁵⁷
Over the following years the average FDA review period for new drugs tumbled from thirty months to under seventeen, a neat deal for drug companies that could now count on many hundreds of millions of dollars in sales in exchange for the relatively paltry user fee.
⁵⁸

The rapid review times allowed dangerous drugs to slip through the FDA's fingers, critics complained, with increasing numbers of new drugs found to be life threatening only after they had been ingested by millions. In 1997, the FDA was forced to withdraw two drugs from the market after they injured and killed patients; in 1998, three drugs were withdrawn; in 1999, two were withdrawn; in 2000, no fewer than four drugs were withdrawn.
⁵⁹

The marketplace might have ably punished any drug company that produced meds that were marginally useful or unsafe with lackluster sales. But in 1997 came another regulatory change that circumvented such a correction.

Until 1997, the largest audiences for advertising messages—television viewers—were virtually unreachable for drugmakers. The FDA required that drug ads list, in addition to the therapeutic properties of the drug, all of its concomitant side effects. In a magazine ad, the side-effects list could be dispensed with effectively in the small type along the margins. In a television commercial, though, the list would have to be read out loud in excruciating detail. Few companies would attempt such a feat.

When companies tried, such as Hoescht Marion Roussel, they failed badly. In the early 1990s the company's best-selling prescription allergy drug, the nonsedating antihistamine Seldane, had been criticized for its dangerous side effects when taken in conjunction with other drugs. The FDA had decided not to pull Seldane off the market, despite its dangers, but things were looking bad for Seldane when, in 1993, Schering-Plough released a
similar nonsedating antihistamine, Claritin, which quickly started to pull ahead in sales.

By 1996, Hoescht had a new product to take Seldane's place and counter the Claritin onslaught: the “new and improved” antihistamine Allegra. Six months later the FDA pulled Seldane off the market. Now it was up to Hoescht to “market Allegra . . . aggressively” as the
New York Times
reported, and reclaim its lost market share.
⁶⁰

But how to do it? Hoescht attempted to advertise Allegra on television, but to sidestep FDA requirements the company's Allegra ads never mentioned what the drug was for. The commercials featured a woman inexplicably windsurfing across a field of wheat, as the
Washington Post
reported. The ads were a disaster, mystifying consumers and providing ample fodder for late-night comedy shows.
⁶¹

Then, in 1997, eight months after pulling Seldane, the FDA announced that TV drug ads would no longer have to portray the bad along with the good about new drugs. Instead, television ads could simply mention the very worst side effects, dispensing with the others by suggesting that consumers consult a Web site or call a 1-800 number to find out more. By allowing drugmakers to highlight the benefits of new drugs while sidelining drawbacks, the new rules would allow even marginally useful drugs, when promoted vigorously, to flourish.

“This is very good timing,” enthused a Hoescht spokesperson.
⁶²
Fall ragweed season was approaching. Now the company could run a proper ad campaign, reaching television's mass audiences with their message that Allegra was a better allergy drug than Claritin, better too than the cheap, over-the-counter remedies that many were opting for.

In 1997, Hoescht spent over $50 million advertising Allegra directly to consumers. It was money well spent; Allegra sales promptly doubled. Schering-Plough responded with over $74 million in consumer advertising for Claritin.
⁶³
As the televised war between the antihistamines raged, Americans flocked to their
doctors clamoring for Claritin and Allegra scrips. In the first eight months of 1998, “patient visits to doctors increased 2 percent, [but] visits for allergies rose five times as fast,” the
New York Times
reported.
⁶⁴
By 1999, drugmakers were spending more on hyping prescription antihistamines to consumers than any other class of drugs.
⁶⁵

And yet, a 2002 study that compared Zyrtec, Claritin, Allegra, and other nonsedating antihistamines found no differences in their efficacy. “When choosing a drug . . . for treatment of allergic rhinitis,” the authors concluded, “the preference of the patients might be the one most important factor, because all the new histamine H
₁
-antagonists appear to be comparable in their efficacy.”
⁶⁶

According to drug industry spokespeople and the FDA, the new “direct-to-consumer” advertising craze helped patients get the drugs they needed. “You need to be told by someone that those products are out there or you'll never know,” FDA medical director Robert Temple said to the
Washington Post
in 1997.
⁶⁷
As for health care providers, the new obsession for prescription allergy meds was hard to fathom. “Except for antibiotics,” commented Mark DiGiorgio, a disgusted HMO executive, “we are spending more money on runny noses than anything else.”
⁶⁸

The FDA's relaxation of drug advertising rules did much more than relieve Hoescht's business troubles. In the past, in order to build a market for a new prescription drug, the medical community would first have to be convinced of the necessity of the treatment. The doc-as-gatekeeper served as a skeptical check on drug companies that might try to sell a risky or useless drug. Now drug companies could reach consumers directly with their exhortations to get checked for dangerous new conditions and ask their doctors for brand-name drugs—and not just for medical problems, either, but for social problems, even for cosmetic ones. Soon scores of consumers whom most physicians would deem healthy were exposing themselves to the risks of pharmaceutical
products, further diminishing the risk-benefit ratio of new drugs.

One such product is Viagra, launched by Pfizer in 1998. Pfizer was about to abandon sildenafil, a failed angina drug, when they picked up on its effect on men's erections. The company soon ran trials among men who had been impotent for five years or more. The drug appeared to overcome impotence in 70 to 80 percent of test subjects.
⁶⁹
According to the NIH-funded Massachusetts Male Aging Study, started in 1987, over half of the thousands of forty-to-seventy-year-old men it surveyed had endured an episode or two of failed erections over the previous six months, but only about 10 percent suffered complete erectile dysfunction. Most of these cases were among men who had other health problems—they were older, tended to smoke, were overweight, and had high blood pressure.
⁷⁰
Many such men could be expected to be taking medications such as nitrates and beta-blockers, prescribed to millions for angina and high blood pressure; for them, sildenafil could be downright dangerous. Quitting smoking, changing medication regimens, counseling, exercise, and weight loss, moreover, could safely relieve many of the less severe problems.
⁷¹

And yet it was true, as Pfizer's marketing director put it, that “most men who are 45 or 47 don't have the same erections they had when they were 18.”
⁷²
These men, with a little help from Pfizer, could be convinced they had a treatable disease. In a prominent television ad campaign featuring no less respectable a personage than former senator Bob Dole, Pfizer announced that “erectile dysfunction (ED),” an obscure medical term dusted off to serve as a more palatable euphemism for impotence, was a serious medical condition that afflicted no fewer than thirty million American men.
⁷³
It was, as one executive explained, “brilliant branding.” “And it's not just about branding the drug; it's branding the condition and, by inference, a branding of the patient. . . . We're creating patient populations just as we're creating medicines, to make sure that products become blockbusters.”
⁷⁴
The
vast majority of ED's supposed thirty million sufferers—about 80 percent—suffered only mild to moderate dysfunction, some as little as one episode of erection loss over the previous six months.
⁷⁵

Pfizer defended what critics would later call disease mongering by saying that they were raising awareness about a shameful disease. Many men “really do want to go to their doctors but can't imagine bringing it up,” Pfizer's marketing director for Viagra, Janice Lipsky, said to the
New York Times
in 2004.
⁷⁶
And yet, there was little evidence of any reluctance to seek out Viagra prescriptions. In Britain, for example, diagnoses of erectile dysfunction doubled.
⁷⁷
By 1999, five million men had been prescribed Viagra, bringing in $1 billion in sales for Pfizer.
⁷⁸
Treatment rates for erectile dysfunction soared above other conditions. In heart disease, by way of contrast, only one-third of patients who could benefit from aspirin are prescribed it by their physicians.
⁷⁹

The drug was obviously being used by people who had no impairment whatsoever. As
Playboy
's Hugh Hefner put it, “It's more than an impotence drug: It's a recreational drug. It eliminates the boundaries between expectation and reality.”
⁸⁰
Almost immediately upon its launch, Viagra pills were making the rounds among thrill seekers at dance clubs and sex parties.
⁸¹
Nervous men used the drug for “date protection,” feminist sex expert Leonore Tiefer scoffed. In Taiwan, a campaigning politician distributed the drug for free. In France, restaurants served “beef piccata in Viagra sauce.”
⁸²
If any needy men had somehow escaped a Viagra prescription, Wrigley planned to deliver the drug in an even more appealing form: Viagra-imbued chewing gum.
⁸³

The FDA logged over one hundred deaths linked to Viagra within the eight months following the drug's appearance on the market, suggesting that the drug may have been implicated in between two thousand and ten thousand deaths. (Between 1 percent and 5 percent of adverse effects of drugs are estimated to be reported to the FDA.) “My husband was 65 with several medical problems and taking several other drugs, but he got the same dose as an 18-year-old,” complained the widow of one Viagra casualty.
⁸⁴

Regardless, like Prozac and Mevacor before it, Viagra paved the way for a $23 billion “life-enhancing” drug market—drugs designed not to heal the sick but rather to make the well feel better.
⁸⁵
Prozac had established a $12 billion market for antidepressants. Mevacor founded a $10 billion market for cholesterol-lowering drugs, a market that grew by over 33 percent every year between 1987 and 1992.
⁸⁶

Rival companies predictably jockeyed to muscle into the new markets. But rather than improve upon the trailblazing blockbuster (or trying to improve upon it, failing, and marching forward anyway), many simply resorted to selling copycats. Between 1998 and 2002 “me-too” drugs—those deemed by regulators to offer no advantage over already available drugs—accounted for three-quarters of the new drugs approved by the FDA.
⁸⁷

Not only would the task of developing, testing, and reviewing the copycat drugs further burden already strained health care and regulatory systems, they would intensify the onslaught of drug marketing to dizzying heights. By 1998, drug companies were spending between two and three times more on marketing and administration than they did on research,
⁸⁸
forking over no less than $1.3 billion on advertising directly to consumers.
⁸⁹
The intense marketing says something about the drugs, former
New England Journal of Medicine
editor Marcia Angell says. “Truly good drugs don't have to be promoted very much. . . . Wouldn't the world beat a path to the door of a company that produced, say, a cure for cancer?” Me-too drugs, on the other hand, “require relentless flogging, because companies need to persuade doctors and the public that there is some reason to prescribe one instead of another.”
⁹⁰

Rather than improving upon Mevacor, for example, drug companies launched a plethora of copycat statins. Four years after launching Mevacor, Merck introduced its cousin, simvastatin (Zocor). That same year Bristol-Myers Squibb released its pravastatin (Pravachol). Pfizer soon offered atorvastatin (Lipitor), followed by Bayer's cerivastatin (Baycol) and AstraZeneca's rosuvastatin (Crestor).
⁹¹