Vioxx – good for what pains us?

This first of three columns about the safety of our prescription drugs focuses on how the current system of pharmaceutical marketing and production brought us the Vioxx fiasco.

Before its manufacturer’s pants get sued off we ought to thank the painkiller Vioxx for showing us that the process of ensuring the safety of our prescription drugs is an emperor with less clothing than a Victoria’s Secret lingerie model. With any luck, however, that will change. When the lawyers are done suing, the politicians are done pontificating and the patients are done suffering, the process for ensuring prescription drug safety will hopefully have undergone an “extreme makeover.”

Until then, we are stuck with the current system of high-pressure production of mass-marketed blockbuster drugs and little post-marketing surveillance for side effects, a system in which Vioxx was a predictable disaster just waiting to happen. Here is why.

First, our pharmaceutical companies are progressively dependent for their profits on the manufacture and sales of hot drugs such as Vioxx ($2.5 billion in annual sales for Merck) and similar drugs Celebrex and Bextra (combined $4.8 billion in annual sales for Pfizer). The companies are under tremendous pressure, primarily from stockholders, to make big profits, they have fewer drugs likely to make big profits in their research and development pipelines than in the past, and drugs such as Vioxx are corporate lifesavers. Vioxx sales alone accounted for 20 percent of Merck Pharmaceutical’s profits in 2003.

This reliance on a few blockbuster drugs means patient safety jockeys with corporate profits as the manufacturers’ priority in decisions about drug marketing. If Merck had highlighted a significant safety issue with Vioxx early on, the drug would have lost the main reason for its success over rivals, that being its lower risk of stomach bleeding as a side effect.

Its side effects and its withdrawal from the market in September 2004 will cost Merck an estimated $14 billion in lawsuits and lost sales, and the company lost $28 billion in stock value when investors heard the bad news about Vioxx, according to a recent article in the New England Journal of Medicine (NEJM). Safety problems with a drug such as Vioxx can shake a drug company to its financial core.

That is not to suggest when the safety issue is clear drug companies will not act appropriately. Rather, it is to suggest that unless forced to do so they may hesitate to pull a drug from the market, or broadcast side effects and thereby cause doctors to prescribe the competition. It is to suggest drug companies will struggle when having to decide between erring on the side of patient safety vs. erring on the side of prescription sales. It is to explain why, according to The Wall Street Journal and The New York Times, it is alleged that Merck may have trained its sales force to avoid directly answering questions from physicians about the increased risk of heart attack in Vioxx users.

Merck had indications of potential problems with Vioxx several years ago but vigorously resisted efforts by others to warn doctors and patients, according to articles in the The Journal and The Times. The same thing may have happened with other drugs ultimately withdrawn from the market by other manufacturers, as documented in a recent NEJM series of articles about Bayer’s cholesterol-lowering drug Cervistatin. Last year the attorney general of New York had to take legal action to force another drug manufacturer to reveal information about the potential increase in suicide risk for depressed teenagers taking its antidepressant drug.

On the other end of the pipeline to the consumer is one more huge problem in the safety system; there is no formal system to look for unanticipated medication side effects once a drug is on the U.S. market. In fact, I think my dog tracks Dunkin’ Munchkins coming into the house better than we track prescription drug side effects in this country. Currently, drug companies don’t have to go looking for side effects; they just have to wait to hear about them. Nor does the Food and Drug Administration systematically look for side effects once a drug is on the market.

The post-marketing side effect surveillance “system” that does exist relies on doctors and patients to identify side effects and voluntarily report them to – guess who? – the manufacturer of the drug. The manufacturer is then supposed to report the side effects to the FDA, which in turn makes recommendations about the drug’s marketing, use, the need for new studies of safety, or even market withdrawal, in order to ensure our safety.

That means a company is spending millions on marketing a new drug at the same time it is supposed to be looking vigilantly for unanticipated side effects, putting it in the difficult position of looking for the bad news side effect needle nobody wants to find in the middle of the new drug marketing “hypestack.” Prompted by the Vioxx mess, however, the FDA has recently proposed some improvements in post-marketing surveillance for side effects.

With billions of dollars on the line and competitors nipping at your heels, now imagine you are Merck. You are accumulating side effect reports and now must decide if the growing noise about a problem with Vioxx is enough to make you shoot a huge hole in your company’s financial bottom line by reporting the side effects to the FDA and telling doctors Vioxx has a big safety problem.

The match to the gas of this combustible mix of companies financially dependent on the success of big drugs and a poor process for collecting side effect data is how prescription drugs are now marketed in the United States, and especially how they are marketed directly to the consumer.

For a drug such as Vioxx, millions of dollars in marketing to doctors and patients means that within a few years of the drug’s entry into the market, millions of patients may be taking it without the benefit of systematic monitoring for side effects. The huge volume of users never used to happen so fast; a drug took much longer to hit the big time and reach millions of patients. Within a few years of it coming on the market, 20 million people were taking Vioxx. Another 30 million were taking its competitors, Celebrex and Bextra (both of which may have some of the same side effect problems as Vioxx, according to recent studies).

A weak system of side effect monitoring and an explosion in numbers of patients taking a medication means an unanticipated side effect can harm thousands before the skimpy safety system identifies the problem, the manufacturer reports it, and the FDA takes action. One FDA scientist has estimated that Vioxx caused 27,000 deaths and heart attacks before it was eventually pulled from the market.

If there is to be any consolation for the thousands harmed by Vioxx it is this: The system will be changed as a result of the Vioxx train wreck. We are likely to see changes in how drugs are marketed, how their pre-market safety record is reviewed, how their post-marketing safety is monitored, and how the FDA works.

The result should be a smaller number of American lives lost each year due to side effects of all prescription drugs, a number currently in the thousands. While that makes Vioxx a good medicine for what has ailed our prescription drug safety system, for those who took it or prescribed it Vioxx was a very bitter pill to swallow. I will never prescribe it again, no matter what Merck and the FDA say about its safety.

Upcoming columns:

Part 2 (March 15): The FDA – what it needs to change to protect us

Part 3 (March 29): The patient – what we need to change to protect ourselves

Erik Steele, D.O., a physician in Bangor, is chief medical officer of Eastern Maine Healthcare Systems and is on the staff of several hospital emergency rooms in the region.