| Painkiller Decision Suggests Shift In FDA's Risk-Benefit Equation
By Marc Kaufman
Washington Post Staff Writer
Monday, April 11, 2005
The Food and Drug Administration's dramatic decision Thursday to rein in the use of a wide array of popular painkillers reflects a broader shift at the powerful agency, which has been battered by six months of controversy over its handling of drug safety issues, say observers in academia and industry and public health advocates.
Certain drug risks that used to be acceptable to the agency have become unacceptable, and benefits that usually guaranteed approval of a new drug are no longer a sure bet -- but whether that is good or bad depends on an observer's viewpoint.
The FDA told the maker of Bextra to withdraw it last week due to risks. (Tannen Maury--Bloomberg News)
"I would say this is a major decision, with the FDA taking a welcome stand for public health," said Curt Furberg of Wake Forest University, a member of the FDA advisory panel that met in February to assess arthritis drugs and an advocate of greater emphasis on drug safety.
"Will they continue like this when the pressure is gone and the next unsafe drug comes along?" he asked. "I'll hold judgment. But for now, I'm surprised and pleased."
Sam Kazman, chief counsel of the Competitive Enterprise Institute, also said the decision was significant -- but not a good one. He said it was surprising that the decision was made by a business-friendly Republican administration closely aligned with the drug industry, but not shocking, given the FDA's history.
"The traditional FDA response to criticism is to revert to deadly overcaution," Kazman said. "When the agency is criticized about a drug, its natural reaction is to withdraw it and become more cautious about approving others in the future. . . . It seems pretty clear now that the pendulum has swung pretty far to the risk-averse side."
The agency's biggest decision last week was to tell Pfizer Inc. to withdraw its arthritis drug Bextra because of concern that it caused increased heart attacks, strokes and a potentially fatal skin disease. The agency also said it would require tougher safety warnings on all anti-inflammatory drugs in the broad class that includes such popular medications as Celebrex, Mobic, Aleve and Motrin.
Bextra is in the same narrower class of drugs as Merck & Co's Vioxx, the blockbuster COX-2 inhibitor pain reliever whose withdrawal from the market in September started the past six months of FDA turmoil. Legislators and others have accused the agency of being too slow in responding to signals that Vioxx could, like Bextra, cause increased rates of heart attacks and strokes.
Although Merck initiated its Vioxx withdrawal, Pfizer withdrew its drug only reluctantly last week and voiced concern that the FDA was changing how it judges the value of medications.
"What worries me a little bit is that because of the public concern over safety, which I'm not saying is misplaced but is sometimes misdirected, they will raise the hurdles on safety much higher than they will on efficacy advantages," Pfizer chief medical officer Joseph Feczko told the Wall Street Journal on Thursday. "The balance may tip too far on risk and away from benefit."
That balance between the risks of a drug or medical device and its benefits is the central question before the FDA.
Drug companies, public health advocates and financial analysts are looking for signals to suggest which way the agency is leaning, reading tea leaves that would show a slight tipping of the balance in favor of emphasizing drug risks or benefits. All drugs have both, and a billion-dollar drug approval (or withdrawal) can turn on which tendency is in ascendance.
In the late 1990s, the agency responded to safety concerns by withdrawing 10 drugs within three years. But until the Vioxx withdrawal, only one other drug had been pulled since the Bush administration began, leading some to conclude that the agency had made a quiet policy change that emphasized "benefit" and sought to manage "risk" less intrusively.
But last week's decision did not require intense scrutiny to understand -- the FDA plainly said that the potential benefits to patients from Bextra carried less weight than the potential risks, especially because a similar drug with fewer risks (Pfizer's Celebrex) was still on the market.
"They've taken a clear stand, a strong stand, and they deserve some credit for that," said Alastair Wood of Vanderbilt University, the chairman of the 32-member February advisory panel on anti-inflammatory drugs. Like Furberg, he had advocated removing Bextra from the market, but the panel narrowly voted in favor of keeping it available. The FDA rejected the panel's recommendation.
"I just hope [the FDA] won't allow itself to be beaten down now that it's reasserted its public health role," Wood said. "This is a tough climate for aggressive regulation."
The Pharmaceutical Research and Manufacturers of America, which represents the brand-name drug industry, does not comment on specific FDA decisions about individual drugs. But it, too, saw a possibly significant change in FDA decision-making last week and found it worrisome. Drugmakers have been generous donors to President Bush's campaigns, and the industry's needs have been important to the administration.
"It's fair to say we're always concerned whenever a drug gets withdrawn from the market, especially if it may lead to a perceived shift in the risk-benefit evaluation," said Alan Goldhammer, the group's associate vice president for regulatory affairs. "When we meet with the FDA, it's often to highlight the fact that the patient's needs have to be respected, and patients need new therapies to treat critical medical issues."
Wood and others said that they believe the intense public attention on the Vioxx withdrawal and troubles that followed -- as well as some strong criticism from Congress of FDA actions and inaction -- played a role in the agency's tough ruling last week. Influential members of Congress, including Senate Finance Committee Chairman Charles E. Grassley (R-Iowa), are pushing for a more independent drug-safety office within the FDA, and the agency has to show that it can respond aggressively to safety concerns if it wants to succeed in fighting off long-term structural changes.
Some lawmakers say that the problem is greater than can be fixed by recalibrating the agency's risk-benefit equation and that the FDA must be restructured.
"The FDA and the companies it is charged with regulating appear to have a very close relationship that may be impeding the ability of the agency to credibly evaluate and regulate serious drug problems," said Rep. Rosa L. DeLauro (D-Conn.). "Congress must consider reorganizing FDA to assure that the individuals being served are the patients of the United States."
Others see the drug industry using its current troubles to make better and safer products. Since the Vioxx withdrawal, the private Bethesda company United BioSource Corp. has seen a doubling in its business of studying how drugs on the market are being used and what unexpected problems might be arising.
Chief Executive Ethan Leder said many drug firms "want to be able to demonstrate their products are safe in the real world, and to understand better what possible risks patients might have so that information can be shared. . . . These post-market studies were not always where companies wanted to invest resources before, but they really want to know the answers now."
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