FRIDAY, Jan. 21, 2005 (HealthDayNews) --
The now-infamous pain relievers known as Cox-2 inhibitors were overprescribed long before their current problems came to light, a new study concludes.
The research, published in the Jan. 24 issue of the Archives of Internal Medicine, finds that many people may have been paying more than needed and may have been unnecessarily exposed to side effects.
Most of the growth in Cox-2 use between 1999 and 2002 came among patients who were least likely to benefit, namely those without a high risk of gastrointestinal (GI) complications, according to the study. Cox-2 inhibitors were developed for patients who had gastrointestinal problems with over-the-counter pain relievers, such as aspirin, ibuprofen and naproxen.
The expanded use of a drug, which some call "therapeutic creep," isn't limited to Cox-2s.
"Pharmaceutical innovations are rarely adopted uniformly among those who stand to benefit the most from their selective advantage. The Cox-2s are not the first and they won't be the last," said Dr. G. Caleb Alexander, senior author of the study and an instructor of medicine at the University of Chicago.
"We need to recognize this and think more about it, both with regard to research, but also health-care policy and regulation," he said. The study was done in conjunction with researchers at Stanford University.
While traditional nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen and naproxen increased the risk of gastrointestinal bleeding and stomach ulcers over the long term, the Cox-2s, introduced in 1999, minimized this risk while providing the same amount of pain relief.
The first downside, however, was that the new drugs cost 10-to-15 times as much as their older cousins, Alexander said.
The second downside came to light in September 2004, when Merck & Co., which makes Vioxx, removed the Cox-2 from the market after indications that it increased the risk of heart attacks. There have since been similar concerns about Celebrex, another Cox-2 made by Pfizer Inc., although that drug is still on the market.
The current study, which began before the controversy erupted, used national surveys of patient visits to their doctors' offices to compare NSAID and Cox-2 prescriptions with treatment guidelines.
Cox-2s were prescribed for all types of patients, although the guidelines specified that patients with "low" or "very low" risk of GI problems receive traditional NSAIDs. In 1999, 12 percent of patients at very low risk (1.7 million people) received Cox-2 prescriptions. That number rose to 40 percent of low-risk patients (7.6 million) in 2001 before turning down slightly in 2002. Sixty-three percent of the growth in Cox-2 use was in patients with lower levels of risk. The remaining 37 percent came from patients who were most likely to benefit.
In general, much of the growth may have been spurred by direct-to-consumer advertising. "Perceptions of benefit are one of the key drivers to the speed with which a new innovation diffuses throughout a population," Alexander said. "Heavy marketing and promotion of these drugs may have contributed to a greater perception of benefit than actually existed."
Outside experts pointed out that the study did not take into account the difficulties associated with evaluating risk. "There's probably some truth to it, but it's a little bit exaggerated," said Dr. Todd Schlifstein, an assistant professor of rehabilitation medicine at New York University School of Medicine. "There are a lot of relative risk factors including alcohol use, smoking, age and aspirin use." Also, the risks vary depending on whether a person will be using the drug long-term or short-term, he added.
Cost is also relative. "The cost can be $30,000 a bleed [hemorrhage]. That pays for a couple of pills," Schlifstein said. "It's always easy to play Monday-morning quarterback and say 'woulda, coulda, shoulda' but you don't know how many people would have bled."
Alexander acknowledged this aspect of medicine can be tricky. "Knowing how to navigate that for any individual patient is tricky," he conceded.
But he and the author of an editorial in the same issue of the journal feel the U.S.'s post-marketing surveillance system for drugs needs to be improved.
"I don't think anyone would expect that, at the time of approval, we'll have perfect information about the safety and effectiveness for a given drug," Alexander said. "It's not so much the dramatic redesign of the approval process, but the larger issues that have to do with postmarketing regulation and oversight."
More information
The U.S. Food and Drug Administration has a public health advisory on NSAIDs.
