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Your Dangerous Drugstore

1.

On April 5, 2006, a New Jersey jury found that Merck’s arthritis drug Vioxx caused John McDarby, a seventy-seven-year-old retired insurance agent, to suffer the heart attack that left him debilitated in 2004. (The drug was not blamed for the heart attack of a second plaintiff in the same case.) The jury also found Merck guilty of consumer fraud for not warning doctors and the public of the drug’s cardiovascular risks. McDarby and his wife were awarded $4.5 million, plus another $9 million in punitive damages because the company was found to have misled the US Food and Drug Administration (FDA). Merck now faces about ten thousand similar lawsuits, and has vowed to fight every one of them. So far, there have been verdicts in four cases—two for Merck and two against (the McDarby case and an earlier one in Texas, in which the plaintiff was awarded $253.5 million, which under Texas law must be cut to $26.1 million).1 If there are more losses, and the chances are there will be, Merck, despite its defiant talk, may ultimately have to try to reach a settlement instead of fighting each case.2

The defeat was not just a loss for Merck, but for the industry as a whole, which has seen its reputation plummet in the past few years. Polls show that among American businesses, the pharmaceutical industry now ranks near the bottom in public approval—above tobacco and oil companies, but well below airlines and banks and even insurance companies. This situation contrasts sharply with the generally high regard in which the industry was held just a few years ago.3

There are three main reasons for the drop in public esteem. First, people are growing increasingly skeptical about the industry’s justifications for its high and rapidly escalating prices. To many, it looks more like simple profiteering than what the industry claims it is—a necessity to cover high research and development costs. People are beginning to realize that even after the pharmaceutical industry’s much-vaunted R&D expenditures, it still has enough left over to make it consistently one of the most profitable industries in the US. Second, as more people began to purchase drugs from Canada in recent years, it became generally well known that prices in the US are much higher than in other countries. While the industry claims that other countries are “free riders,” it seems to many Americans that it is the drug companies who are free riders. Finally, many older people have become all too aware of the fact that the new Medicare drug benefit, as a result of pressure from the powerful pharmaceutical lobby, specifically prohibits Medicare from using its huge purchasing power to bargain with drug companies for lower prices (even though it is allowed to regulate doctors’ fees and hospital payments). This prohibition adds to the disillusionment with a bill that is not only weirdly byzantine but provides far less help than it might, and it increases resentment toward the pharmaceutical industry.

Much of what is wrong with the industry is explained in several recent books. They include Merrill Goozner’s The $800 Million Pill, which shows that most innovative research on serious diseases like cancer and HIV/AIDS is done not by drug companies but in government and university labs. Jerry Avorn’s Powerful Medicines discusses the risks and benefits of the drugs themselves, and shows that many of them fall far short of their marketing promises. John Abramson’s Overdosed America presents a clinician’s view of the misinformation that leads doctors to prescribe unnecessary and possibly harmful drugs. Jerome Kassirer’s On the Take explains how the medical profession has allowed itself to be seduced by the billions of dollars lavished on it by the drug companies (for example in subsidizing medical meetings of all types). Sharna Olfman’s No Child Left Different takes a critical look at the promotion and overuse of psychoactive drugs in children. Selling Sickness, by Ray Moynihan and Alan Cassels, explains how the pharmaceutical industry increases sales by convincing essentially normal people that they have chronic conditions (such as erectile dysfunction) that require lifelong drug treatment. Although each of these books emphasizes different parts of the system, they are remarkably consistent when they overlap, and together they make a damning case, not just against the industry but against our entire system for developing, testing, and using prescription drugs.4

The Vioxx story exemplifies many of the problems.5 It first came to public attention on September 30, 2004, when Merck announced it was pulling Vioxx from the market, citing a clinical trial that showed it doubled the risk of heart attacks and strokes.6 Vioxx had been heavily promoted to both doctors and the public. The “direct-to-consumer” ads on television featured 1976 Olympic gold medalist Dorothy Hamill skating effortlessly across an outdoor rink to the Rascals’ “It’s a Beautiful Morning”—presumably free of arthritis pain, thanks to Vioxx. At the time the drug was withdrawn, an estimated 20 million people had taken Vioxx, and it had yearly sales of $2.5 billion. The withdrawal of Vioxx was front-page news and caused great public concern—both among those who felt the drug was uniquely effective in relieving their arthritis symptoms and among those who feared they might have a heart attack or stroke because of the drug. Merck’s stock price fell by more than a quarter on the day of the announcement, and market analysts began to speculate about the company’s uncertain financial future and legal liabilities.

Attention immediately turned to Pfizer’s Celebrex and Bextra.7 All were in the same class of drugs, called COX-2 inhibitors, and there were two more in late-stage development, Merck’s Arcoxia and Novartis’s Prexige.8 The first of them, Celebrex, which had preceded Vioxx on the market by a few months, was an even bigger success, with sales of $3.3 billion. The others were what are known as “me-too drugs”—additional drugs in the same class. An editorial in The Wall Street Journal, loyal as always to the pharmaceutical industry, found something to celebrate. “The Vioxx withdrawal,” it said, “shows why choice in ‘me-too’ drugs is a good thing.”9 I wrote a letter to the editor pointing out that it was premature to conclude that Celebrex and Bextra were in the clear. “Since they are so much like Vioxx,” I said, “I would not bet my ice skates that they are not eventually shown to have similar risks.”10

It didn’t take very long. Within months, there were reports that Celebrex and Bextra also increased the risk of heart attacks and strokes, at least in some patients at some doses.11 But Pfizer announced that, unlike Merck, it would leave the drugs on the market, although it would stop advertising them to consumers, because, as its CEO explained to a television reporter, whether and how to use the drugs were “complicated” matters that ought to be left to doctors in discussion with each patient. (He did not explain why that very sensible advice should not apply to other prescription drugs promoted directly to the public.)

As confusion grew, the FDA appointed a special advisory panel to hold hearings and advise it about how to handle the situation. There were several possible courses of action for the FDA. For example, all the COX-2 inhibitors could be pulled from the market immediately. Or Celebrex, which seemed safer than the others at usual doses (it acted like a weaker version of Vioxx), could be allowed to remain. (As is often the case with me-too drugs, apparent differences have a lot to do with the dose.) Or they could all be left on the market, including Vioxx, but with some new guidelines restricting their use.

The FDA advisory panel consisted mainly of members of two standing advisory committees—one for arthritis and one for drug safety. During the hearings and deliberations, which were public, there were emotional testimonials from patients who claimed that one or another of the COX-2 inhibitors had produced spectacular results after other types of painkillers had failed. The hearings lasted for three days in mid-February 2005, and the final decision was prominently reported in the press.12 Although the panel agreed that COX-2 inhibitors as a class did indeed increase the risk of heart attacks and strokes, it concluded that the benefits outweighed the risks (the vote was close in the case of Vioxx and Bextra). It therefore recommended that Celebrex and Bextra remain on the market and that Vioxx be allowed to return, perhaps with strong warnings on the labels for all three, and a moratorium on ads that appealed directly to consumers.

On April 7, 2005, however, following revelations that many panel members had financial ties to Merck or Pfizer, the FDA, which usually takes its advisory committees’ advice, decided differently. As expected, it announced that Celebrex could remain on the market, with a strong warning on its label. But the agency asked Pfizer to take Bextra off the market, and indicated that if Merck wanted to bring Vioxx back, it would have a difficult battle.

The story of the approval and marketing of the COX-2 inhibitors illustrates nearly every major criticism of the pharmaceutical industry made in my book The Truth About the Drug Companies: How They Deceive Us and What to Do About It. Among other things I criticize the lax standards for approval of drugs, the conflicts of interest that pervade the system and influence decisions, the slowness of both industry and the FDA to respond to danger signals, the power of the industry’s huge marketing campaigns, and the baseless justifications for me-too drugs.

In late 1998 and early 1999, Celebrex and then Vioxx were approved by the FDA. They were given rapid “priority” reviews—which means the FDA believed them likely to be improvements over drugs already sold to treat arthritis pain. Was that warranted? Neither drug was ever shown to be any better for pain relief than over-the-counter remedies such as aspirin or ibuprofen (Advil) or naproxen (Aleve). But theory predicted that COX-2 inhibitors would be easier on the stomach, and that was the reason for the enthusiasm. As it turned out, though, only Vioxx was shown to reduce the rate of serious stomach problems, like bleeding ulcers, and then, mainly in people already prone to these problems, a small fraction of users. In other words, the theory just didn’t work out as anticipated.

Furthermore, people vulnerable to stomach ulcers could probably get the same protection and pain relief by taking a proton-pump inhibitor (like Prilosec) along with an over-the-counter pain reliever.13 So the COX-2 inhibitors did not really fill an unmet need, despite the one seemingly attractive claim made in favor of them. Nevertheless, the FDA acted as if they did, by giving these drugs expedited review and approval.

In my book I discussed the conflicts of interest pervading the FDA, including the fact that many members of FDA advisory committees are paid consultants for drug companies. Although they are supposed to recuse themselves from decisions when they have a financial connection with the company that makes the drug in question, that rule is regularly waived. With that in mind, I checked the minutes of the 1999 advisory committee meeting that led to the approval of Vioxx. Sure enough, four of the six members, including the chairman, were granted waivers because they had a “potential for a conflict of interest.”14

  1. 1

    For full accounts see Alex Berenson, “A 2nd Loss for Merck Over Vioxx,” The New York Times, April 6, 2006, and “Vioxx Jury Adds More in Damages,” The New York Times, April 12, 2006.

  2. 2

    Merck recently lost another case, when a jury in Rio Grande, Texas, awarded $32 million (which must be reduced to $8 million) to the family of a man who died of a heart attack after taking Vioxx.

  3. 3

    See Kaiser Family Foundation news release, “Americans Value the Health Benefits of Prescription Drugs, But Say Drug Makers Put Profits First, New Survey Shows,” February 25, 2005, www.kff.org/kaiserpolls/pomr022505nr .cfm.

  4. 4

    Merrill Goozer, The $800 Million Pill: The Truth Behind the Cost of New Drugs (University of California Press, 2004); Jerry Avorn, Powerful Medicines: The Benefits, Risks, and Costs of Prescription Drugs(Knopf, 2004); John Abramson, Overdosed America: The Broken Promise of American Medicine (HarperCollins, 2004); Jerome P. Kassirer, On the Take: How Medicine’s Complicity with Big Business Can Endanger Your Health(Oxford University Press, 2004); No Child Left Different, edited by Sharna Olfman (Praeger, 2006); Ray Moynihan and Alan Cassels, Selling Sickness: How the World’s Bigest Pharmaceutical Companies Are Turning Us All into Patients (Nation Books, 2005).

  5. 5

    I tell the story in the epilogue of the paperback edition of my book, The Truth About the Drug Companies: How They Deceive Us and What to Do About It(Random House, 2005).

  6. 6

    For full accounts of the withdrawal, see Gina Kolata, “A Widely Used Arthritis Drug Is Withdrawn,” The New York Times, October 1, 2004, and Alice Dembner, “Maker Takes Vioxx off Market,” The Boston Globe, October 1, 2004.

  7. 7

    Andrew Pollack, “New Scrutiny of Drugs in Vioxx’s Family,” The New York Times, October 4, 2004.

  8. 8

    One of the causes of pain and inflammation are chemicals in the body called prostaglandins. Many over-the-counter arthritis drugs act by inhibiting two enzymes, called cyclooxygenases, responsible for the effects of prostaglandins. But the first of these enzymes also protects the lining of the stomach. COX-2 inhibitors were designed to inhibit only the second, thus protecting the stomach while reducing pain.

  9. 9

    A Vioxx Elegy,” The Wall Street Journal, October 1, 2004.

  10. 10

    Marcia Angell, “Merck Downplayed Risks of Its Vioxx,” The Wall Street Journal, October 7, 2004.

  11. 11

    As usual, some of the best reporting about the pharmaceutical industry came from the New York Times reporter Gardiner Harris. See his stories “Drug Trial Finds Big Health Risks in 2nd Painkiller,” The New York Times, December 18, 2004, and “New Study Links Pfizer’s Bextra, Similar to Vioxx, to Heart Attacks,” The New York Times, November 10, 2004.

  12. 12

    Gardiner Harris, “FDA Is Advised to Let Pain Pills Stay on Market,” The New York Times, February 19, 2005.

  13. 13

    Proton-pump inhibitors are drugs that inhibit the normal secretion of hydrogen ions (protons) by the stomach. That interferes with the formation of stomach acid, which in turn reduces the risk of heartburn and ulcers.

  14. 14

    For a transcript of that meeting, see www.fda.gov/ohrms/dockets/ac/cder9t.htm#Arthritis.

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