Unraveling the Cox-2 Debacle

A NextGen Perspective
(Continued from previous page)

In the face of accumulating scientific evidence, criticism from Graham, and a growing national firestorm, the FDA convened an advisory committee to evaluate the safety of the COX-2 drugs in February 2005. [12] The panel agreed that all three of the major COX-2 inhibitors (Vioxx, Celebrex, Bextra) raised the risk of cardiovascular problems. Yet the panel approved all three drugs to remain on the market (although Vioxx and Bextra were approved by very slim margins). [13] Some saw the panel's decision as regulators' attempts to allow doctors to calculate with their patients the risks and benefits of the COX-2 drugs. But Angell has a different explanation.

"As we learned, 10 of the 32 members of the special advisory panel that recommended that the COX-2 inhibitors remain on the market worked for the companies that made them. If their votes had been discounted, the panel would have recommended that Vioxx and Bextra be withdrawn." [14] In other words, the pharmaceutical industry, active at first in gaining a rapid approval for the COX-2 drugs, had now apparently reached into the judge's chambers in order to protect its products.

The result, says Angell, is a scary situation where we can never be quite sure about the drugs we use. "Unfortunately, it's very difficult to be confident that newly approved drugs are safe," she said. "As we've learned over the past couple of years, drug companies may suppress unfavorable results from clinical trials they sponsor. Even the trials they do publish are often designed in such a way that their drugs look safer or more effective than they probably are." [15]

There are overwhelming incentives for drug companies to behave in such a way. In the opening chapter of her book, The Truth About the Drug Companies: How They Deceive Us and What to Do About It, Angell describes the pharmaceutical industry as a "$400 billion megacolossus" that is "used to doing pretty much what it wants to do." Such a massive industry is likely to use its weight to protect its assets. For the first quarter of 2004, before the news of the dangers of the COX-2's had spread, Pfizer made more than $1 billion on the sale of Celebrex and Bextra. This year, in a comparable time period, that revenue had dropped to a mere $467 million. Giving up those profits is not an easy thing to do.

One of the primary reasons for the great profitability of the COX-2 drugs was that direct-to-consumer advertising brought them within sight of everyone with a television. Studies showed that some of the highest usage of COX-2 drugs was among those with the lowest risk of gastrointestinal problems: in other words, among those who could have taken the older and cheaper over-the-counter drugs. [16] The inflated demand at one point allowed COX-2's to seize 40 percent of the anti-inflammatory market from the traditional painkillers. [17] Ironically, the inflated number of people using COX-2's as a result of the successful direct-to-consumer advertising may have been a key factor in the drugs' misfortune.

Direct-to-consumer advertising was not the only factor in the current COX-2 controversy. But the degree to which prescription drugs are advertised to Americans does shape American drug consumption. "The pharmaceutical industry is theoretically limited in its advertising," Angell said. "The FDA has regulatory authority over the content of ads and is supposed to ensure that they are accurate and balanced. But the agency has neither the resources nor the will to do that. The U.S. and New Zealand are the only advanced countries that permit direct-to-consumer ads." [18]

With more consumers getting their drug information from television, doctors have a responsibility to act as a counterweight to the drug companies' marketing schemes. In light of the COX-2 controversy, this is a responsibility that many doctors seem to have abandoned, finding it easier to acquiesce to the coinciding demands of the drug companies and their patients. "The pharmaceutical industry, with its vast wealth and power, has been successful at co-opting nearly every institution that might stand in its way, including the medical profession. The profession has abdicated its responsibility to educate doctors in the use of prescription drugs, and generally permitted drug companies to interject themselves inappropriately in the practice of medicine." [19]

The future of the COX-2 drug family is uncertain. In a move that appears to be a response to its critics, the FDA decided on April 7 to suspend sales of Bextra because of concerns about cardiovascular risk and skin dangers. Sales of the drugs have slipped significantly. There is also concern that in the general backlash against the existing COX-2 drugs, researchers will shy away from experimenting with new treatments that utilize their anti-inflammatory attributes. Already the National Institutes of Health has suspended trials using Celebrex to fight colon cancer.

For a pre-med student such complications and dilemmas may seem well removed from the goal of medicine. But with a good set of discerning eyes, a heart in the right direction, and a desire for the truth, a doctor can wade through this slough of despair. As Dr. Angell put it, "the best thing medical students can do is resist the blandishments of the industry, which can look very inviting when students are tired and overworked and worried about their debts. But there really is "no free lunch." Drug companies expect something in return (they are not charities, after all), and the evidence is overwhelming that they get it. Doctors, as well as the public, come to believe that the newest, most expensive drugs are better than older, cheaper ones, but there is usually no scientific evidence to that effect."

Chris Catizone is an Associate Editor of the Next Generation and a member of the Harvard College Class of 2006.