November 23, 2004
Medical Journal Calls for a New Drug Watchdog
By DENISE GRADY, NY TIMES, November 23, 2004

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The United States needs a better system to detect harmful effects of drugs already on the market, and it should be independent of the Food and Drug Administration and the drug industry, medical researchers and journal editors said yesterday.

Arguing that it was unreasonable to expect the same agency that approves drugs to "also be committed to actively seek evidence to prove itself wrong," the editors of The Journal of the American Medical Association recommended that the nation consider establishing an "independent drug safety board" to track the safety of drugs and medical devices after they were approved and in widespread use.

The idea has been proposed several times, usually after a spectacular drug imbroglio like the recent withdrawal of the popular arthritis drug and painkiller Vioxx after it was linked to heart attacks. But the earlier proposals went nowhere.

This time around, as in the past, the industry and the drug agency reacted by challenging the need for a new safety board.

"It is not at all clear that there is need for change," Jeff Trewhitt, a spokesman for PhRMA, the trade group for drug makers, said.

Dr. Sandra Kweder, deputy director of the Office of New Drugs at the F.D.A., said a safety board was not necessary because "we consider our office of drug safety independent of the office of new drugs."

But both also left open the possibility of change in the future, depending on the findings of a study to be conducted by the Institute of Medicine, a branch of the Congressionally chartered National Academy of Sciences, which conducts scientific reviews for the government.

An act of Congress would most likely be needed to establish an independent board to evaluate the safety of drugs after they reach the market. The recommendation for a new safety board appeared in an editorial and in one of several articles that were scheduled for the Dec. 1 issue of the journal but were published online yesterday at www.jama.com.

The articles were released early because of their relevance to recent events: the Vioxx withdrawal and the addition of a strong warning to antidepressants because of evidence that they may raise the risk of suicidal thinking or suicide attempts in teenagers.

Those actions led to Congressional hearings last week and complaints that the drug agency was not moving quickly enough to get dangerous drugs off the market or to warn consumers about risks that emerged after drugs were approved.

Senator Charles E. Grassley, the Iowa Republican who led the hearings, favors an even stronger separation between the F.D.A.'s offices of new drugs and drug safety, a spokeswoman said yesterday. Mr. Grassley could not be reached for comment on the proposal for a new safety board.

The nation's current system for tracking drug side effects, called Medwatch, is rife with inadequacies, the editors of the journal wrote. The major problem, they said, is that drug makers are the ones who collect and evaluate most of the information on side effects from their own products and then report it to the F.D.A.

The companies "may be tempted to conceal" unfavorable data, the editors wrote, and they and the drug agency may be too slow to order studies to follow up hints of trouble.

Another flaw the editors cited is the system's reliance on voluntary reports from doctors, which means that most adverse effects probably go unreported. In addition, they said, most of the reports are of poor quality and cannot be used to determine how common side effects are or whether particular problems resulted from medicines or from the illnesses they were meant to treat.

The reports can be used as red flags, particularly if they concern rare conditions that would be hard to explain as anything other than a drug effect. But researchers say a passive system like Medwatch cannot be expected to pick up a drug-related increase in a disease that is already very common, like heart attacks or stroke. Carefully controlled studies are required to detect such problems - and they are not done often enough, researchers say.

The journal editors also noted that although drug companies have agreed to conduct postmarketing studies as a condition of approval for certain drugs, fewer than half the promised studies have been completed and many have not even been started.

Dr. Kweder, of the F.D.A., said, "We have very little authority to make sure those postmarketing commitments are carried out." Legislation would be needed to give the agency that power, she said.

But she said she did not see the need for an independent safety agency, given the separation between the Office of Drug Safety and the Office of New Drugs.

"We believe there is a healthy tension between those offices and there should be," Dr.. Kweder said. But, she added, "We are certainly willing to consider what alternatives there might be or how to facilitate that separation further."

That openness to change, she said, is why the drug agency asked the Institute of Medicine to evaluate its ability to track drug safety.

Mr. Trewhitt, the PhRMA spokesman, also said the F.D.A.'s Office of Drug Safety was independent enough, and noted that it would be doubling its staff by adding 106 officers over the next few years. He said "it would be wise" to wait for the Institute of Medicine's recommendations before making any changes in postmarket safety monitoring.

Other articles in the journal included a contentious exchange between doctors and a lawyer for Bayer over the company's drug Baycol, a cholesterol-lowering statin drug that was taken off the market in 2001 because it caused muscle breakdown in some patients.

The doctors, who acted as expert witnesses for plaintiffs suing Bayer, relied in part on company documents that became public during the case to conclude that Bayer had withheld or delayed releasing data that would have revealed the problems with Baycol and might have led to an earlier withdrawal.

"My judgment is that pharmaceutical companies may have too high a threshold for taking action in a timely fashion to protect the health of the public," one of the experts, Dr. Bruce M. Psaty, a professor of medicine and epidemiology at the University of Washington, said in an interview.

In a published response in the journal, Bayer's lawyer, Joseph D. Piorkowski Jr., denied that Bayer had acted too slowly, and said that the company had acted responsibly by withdrawing the drug voluntarily.

Bayer also issued a statement that said, in part, "The company believes the article is unscientific, lacking in fair balance and objectivity," and questioned the doctors' objectivity because they had worked for the plaintiffs suing the company.

Like the journal editors, Dr. Psaty recommended that an independent safety board be formed, perhaps appointed by Congress, to decide when drugs should be taken off the market.

Not all researchers agree. In another article in the journal, Dr. Brian L. Strom of the University of Pennsylvania School of Medicine said, "Our F.D.A. colleagues can be trusted to do the job, given sufficient resources."

But Dr. Alastair Wood of Vanderbilt University, an expert on drug research and regulation, who did not contribute to the journal, said he thought an independent board was needed.

Dr. Wood said: "When we have a drug problem it's analogous to a plane crashing off the coast of New York City, and being investigated by the air traffic controllers who controlled the flight and the airline flying the plane. They're not bad people, but it's not the way we do things in this country."