Watchdog Group Claims GlaxoSmithKline Misled FDA

Public Citizen accuses drugmaker of hiding danger of popular asthma drug

FRIDAY, Oct. 7, 2005 (HealthDay News) -- Public Citizen has accused GlaxoSmithKline of giving misleading study results to the U.S. Food and Drug Administration on its popular asthma drug salmeterol.

The watchdog group claims the drugmaker was trying to hide the extent to which salmeterol (Serevent) can cause asthma-related deaths. GlaxoSmithKline denies the charge and says they followed FDA protocol and alerted physicians to the potential dangers of the drug.

The debate is played out in two letters in the Oct. 8 issue of The Lancet.

Salmeterol is one of a class of drugs called long-acting beta agonists and is designed to relieve asthma symptoms by opening the airways; however, it is meant to be taken along with an inhaled steroid, which reduces inflammation, the cause of asthma. Another GlaxoSmithKline product, Advair, contains both drugs.

"GlaxoSmithKline misled the FDA, that resulted in the FDA complaining about it and a delay before the FDA realized the increased risk of asthma death from this drug was even larger than they thought," said Dr. Sidney M. Wolfe, director of Public Citizen's Health Research Group. "They [the company] mixed in data that happened after the trial."

"This drug has been given out, presumably, to decrease deaths from asthma, where in fact it increases death from asthma," Wolfe said. "Delays concerning FDA's full understanding of this are reckless and dangerous."

The controversy centers around the company's failure to report that some study results provided to the FDA actually occurred six months after the trial had ended. The 28-week SMART study found an increased risk of asthma-related death among those taking salmeterol.

According to the letter by Wolfe and his colleague Dr. Peter Lurie, deputy director of Public Citizen's Health Research Group, data outside the trial period is tainted, since you don't know if the people in the trial continued on the same drug regimen that they did during the trial. "Having this data made it appear that the risk was lower than it is," he said.

Among Public Citizen's other concerns are that the results of the trial have never been published.

After learning of the problem, the FDA's Pulmonary-Allergy Drugs Advisory Committee recommended in July 2005 strengthening the warning on the labels for both Serevent and Advair. The agency has not yet made a final decision.

"In this case, the FDA cannot be faulted for the fact that the company misled them," Wolfe said. "They bought some extra time for these big-selling drugs, delaying the advisory committee meeting, which should have happened much earlier."

Wolfe believes that neither Serevent nor Advair have a place in asthma treatment. "To say that these drugs are safe when taken with a steroid is just not correct," he said.

"These are not indispensable drugs," Wolfe said. "If someone is adequately treated with steroids, there is really no need for these drugs, particularly when the drugs increase your chance of dying from an asthma attack."

In response, GlaxoSmithKline's vice president of the Clinical North America Respiratory Medicine Development Center, Kathy A. Rickard, says in her letter that the protocol of the 28-week study also was meant to include six months of follow-up. The company says that there were no substantial differences between the results from the 28-week trial and the additional six months of follow-up.

In addition, Rickard says that the trial results have been posted on its clinical trial Web site and submitted to the journal Chest for publication. Furthermore, doctors have been alerted to the potential danger of the drug.

"GlaxoSmithKline has acted responsibly, transparently, and has communicated rapidly through multiple channels to ensure that the findings from SMART were available to health-care professionals and patients," Rickard wrote.

One expert thinks there is less here than meets the eye.

"There is some truth on both sides, but I think GlaxoSmithKline played by the rules," said Dr. David L. Katz, an associate professor of public health and director of the Prevention Research Center at Yale University School of Medicine.

"Consumer watchdogs may be concerned that GlaxoSmithKline did not do enough to highlight the study findings," Katz said. "We can all be thankful for such concerns, as they -- along with the threat of litigation -- help ensure high ethical standards when large sums of money are at stake. But it's easy for such groups to exaggerate wrongdoing, because there is always something more that could have been done to safeguard the public."

The SMART trial and its disclosure have been responsibly handled, Katz said. "Serevent can relieve asthma symptoms, but with a slight increase in the risk of uncommon disease complications, including asthma-related death," he said. "This is not a scandal, merely one of the many risk-benefit considerations that should inform the mutual decisions of patients and their doctors."

More information

The National Library of Medicine can tell you more about salmeterol.

SOURCES: Sidney M. Wolfe, M.D., director, Public Citizen Health Research Group, Washington, D.C.; David L. Katz, M.D., M.P.H., associate professor of public health, director, Prevention Research Center, Yale University School of Medicine, New Haven, Conn.; Oct. 8, 2005, The Lancet
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