Date: Tuesday, March 23, 1999 Subject: IS THE FDA TOO QUICK TO CLEAR DRUGS? > >Is FDA Too Quick to Clear Drugs? >By John Schwartz >When Jo Ann Ottmers began taking her new diabetes medicine, the drug >suddenly made it much easier for the 59-year-old diabetic to keep her >blood sugar levels from rising dangerously high. But soon the Kansas >City, Mo., woman began feeling nauseated and weak. > > Ottmers finally stopped taking the >drug > after discovering on the Internet that > the medicine could cause rare but >> life-threatening liver damage. But her >> health continued to decline, and 16 >> months after she began taking the drug >> she was forced to undergo a liver >> transplant. She has since sued >> Warner-Lambert, the company that makes >> the drug, Rezulin. >> >> Warner-Lambert insists that Rezulin is >> safe if patients are monitored closely. >> Nevertheless, because of dozens of cases >> like Ottmers's ‚ 28 deaths and seven >> liver transplants linked to the drug ‚ >> the FDA this week will consider whether >> regulation of its use should be >> tightened. >> >> The questions about Rezulin, however, >> illustrate a larger debate that is raging >> over the safety of the medicines that >> millions of Americans take every day. >> Pressured by Congress, AIDS activists and >> drug companies in recent years, the >> historically sluggish FDA had to remake >> itself. Today, the agency is approving >> more drugs every year than ever before, >> taking half the time to do it. >> >> Consumer advocates, and even some of the >> agency's own drug reviewers, argue that >> the agency has become too cozy with the >> pharmaceutical industry and too lax, >> putting lives at risk. Five drugs have >> been pulled off the market over the last >> two years ‚ a record for such a short >> time ‚ after dozens of deaths were linked >> to their use. >> >> The FDA insists that its vetting >> processes are still the world's gold >> standard for safety. "I do not believe >> the standards have been lowered," said >> Murray Lumpkin, who heads the agency's >> drug safety programs. "There is no way >> that we will completely eliminate the >> risk from the process ‚ if we have drugs >> with no risks, we will have no drugs." >> >> The record number of drugs pulled off the >> market is, in fact, in line with the >> historic 2 percent to 3 percent >> withdrawal rate for new drugs, said >> Kenneth I. Kaitin, director of the Tufts >> University Center for the Study of Drug >> Development. With so many new medicines >> being approved, Kaitin said, the number >> of withdrawals is bound to climb as well. >> "We're still not any different and not >> any greater than we have been in the >> past," he said. >> >> But even if the rate of problem drugs has >> not increased, drug safety experts say >> the increased pace of drug approvals >> means that more problems are bound to >> make it onto the market. To guard against >> that, drug safety experts argue that more >> should be done to conduct follow-up >> studies on the safety of these drugs >> after they arrive on pharmacy shelves to >> catch problems early. >> >> "My concern isn't these disasters ‚ my >> concern is the disasters that are >> underway that we don't know about," said >> Brian Strom, a professor of medicine at >> the University of Pennsylvania. "No one's >> minding the store." >> >> Critics point out that the FDA's lead >> reviewer of Rezulin, John Gueriguian, >> opposed its approval and was removed from >> considering the application. Gueriguian >> said he found the company's safety >> testing inadequate and its claims of >> efficacy unconvincing. Even more, he >> said, his review of animal studies and >> clinical trials that revealed rare signs >> of jaundice signaled that the drug had >> hidden dangers. Nevertheless, the FDA >> approved the drug in March 1997 with >> exceptional speed because it offered a >> new way to control diabetes. >> >> The FDA said it does not remove reviewers >> because of their positions on drugs but >> would not elaborate on why Gueriguian was >> removed. Warner-Lambert officials say >> Gueriguian used inappropriate language in >> criticizing the company and its >> application during meetings in September >> 1996. An affidavit by a Warner-Lambert >> official supplied to The Washington Post >> by the company referred to a Sept. 25, >> 1996, meeting in which "Dr. Gueriguian >> removed a bottle of what appeared to be >> cologne from his desk and said that he >> had to pour it over the [application] >> because it smelled 'like garbage'í" and >> excrement. "Later during the meeting, he >> said that it had been about a half-hour >> and that 'the [application] was starting >> to smell again' and pretended to pour the >> cologne over the boxes containing the >> [application].'í" >> >> As large numbers of patients began taking >> Rezulin, the liver damage reports started >> to come into the agency's system for >> monitoring drug side effects. As evidence >> mounted that some patients could be >> harmed or even killed by the drug, the >> agency changed the labeling on the drug ‚ >> not once but three times ‚ to require >> more extensive testing of patient liver >> function. Since that time, confirmed >> reports of damage linked to Rezulin have >> dropped, but unconfirmed reports of liver >> damage continue to come into the agency. >> A Washington-based consumer advocacy >> organization, Public Citizen's Health >> Research Group, has filed a petition >> demanding that the agency remove Rezulin >> from the market. >> >> Patients who believe they have benefited >> from Rezulin say they would hate to see >> the drug pulled. "I would half-kill to >> stay on it," said Laura Wilson-Perry of >> Memphis. "But if something came along >> that would regulate my blood sugar in the >> same way, I'd jump to it in a second >> because I don't want to risk liver >> problems." >> >> Drug safety experts say the tests >> designed to ferret out problems ahead of >> time can only detect so much. The tests >> required for new drugs typically involve >> from 1,500 to 6,000 patients ‚ too few to >> catch a drug reaction that might be >> experienced by less than 1 in 10,000 >> patients. The trials also are too brief >> to catch reactions that might emerge over >> years of use. That means the current >> system of testing drugs is fated to miss >> uncommon reactions until it reaches a >> broader market, making the drug-taking >> public guinea pigs in an ongoing >> experiment. >> >> Americans could demand that more patients >> be tested before a drug can be approved ‚ >> say, 100,000 patients to find reactions >> that might affect 1 in 20,000, Lumpkin >> said. And regulators could demand to see >> the effects of a drug taken over years. >> Obviously, however, "there is a cost to >> that ‚ a cost not only in dollars but a >> cost in time" during which patients >> cannot take medicines that might help >> them. >> >> The fact that problems might not be >> detected on the front end of drug >> approval means the agency must do >> everything it can to catch side effects >> after approval, safety advocates say. But >> while the agency is working to upgrade >> what it calls "postmarket surveillance," >> it still depends largely on a system of >> reporting by doctors and companies that >> probably only catches about 1 percent of >> such adverse events, according to Raymond >> Woosley of Georgetown University Medical >> School. Agency officials point out that >> this is still enough to send up a red >> flag for many safety problems, although >> it does not allow a precise accounting. >> >> The FDA is buried under the 150,000 >> reports that flow in each year, agency >> insiders say. And 1992 legislation that >> brought in industry funds to speed up >> review times prohibits the use of that >> money for postmarket surveillance ‚ a >> fight the agency lost against the >> industry, said former FDA commissioner >> David A. Kessler. "That's where we fell >> down," Kessler said. "We didn't go to the >> wall." >> >> In a recent article in the Journal of the >> American Medical Association, Timothy >> Brewer of Harvard University called for >> the FDA to go beyond its current >> reporting system, which relies on doctors >> and companies to report suspected >> problems. Brewer advocates more extensive >> use of data collected by medical >> researchers and others to sift for drug >> reactions. >> >> Woosley goes further. He proposes >> creating a drug safety agency independent >> of the FDA so the regulators who approve >> drugs are not responsible for figuring >> out what they did wrong when disaster >> strikes. "When a plane crashes, you don't >> ask the FAA if their standards are >> wrong," Woosley said. >> >> Another problem, however, is that the FDA >> cannot control how doctors prescribe the >> medications it regulates. Today's health >> care system gives doctors and patients >> less time to discuss medication and its >> risks, and patients increasingly demand >> medicines that they have heard about >> through drug company advertising. So even >> though the agency had explicitly warned >> doctors not to prescribe Duract for more >> than 10 days at a time, physicians >> prescribed it for longer periods; four >> patients died and eight required liver >> transplants before the drug was >> withdrawn. Similarly, the FDA warned >> doctors that Posicor could kill patients >> if taken with some 25 other drugs, yet >> hundreds of patients had life-threatening >> reactions. >> >> "If we're getting to a point where we're >> getting a standard of drug approval that >> says we can only approve drugs after we >> have second-guessed how they will be >> misused and how to keep the misuse from >> happening, that's going to be a very >> difficult standard," said the FDA's >> Lumpkin. >> >> Drug safety advocates urge the creation >> of new programs to better educate doctors >> on the one hand and more systematically >> look for side effects on the other. "We >> still need to get drugs approved more >> quickly," Woosley said. "It's not a >> problem with the drugs, it's a problem >> with the way they're used and a safety >> system that doesn't catch problems >> quickly enough." >> >> Even Gueriguian, who has retired from the >> FDA and now works as a consultant to drug >> companies, believes the agency is merely >> adjusting to a new system of approvals >> and has not gone seriously astray. "If >> anyone says the whole system has gone to >> pot, they are vastly exaggerating," he >> said. >> >> Charles Flexner of the Johns Hopkins >> University Medical School said the FDA >> was right to speed up its processes, but >> "we are making a societal trade-off >> here." More people will be injured from >> unanticipated side effects, Flexner said, >> but at the same time far more people can >> benefit from the presence of new drugs on >> the market. "This is a very tough line >> that the FDA has to walk," he said. >> >> For doctors and patients, the wisest >> course might be to let others take the >> early risk. Gail Povar, a primary care >> internist in Silver Spring, said she >> rarely prescribes a new drug in its first >> year on the market. >> >> When patients demand a new drug, she >> makes sure they understand that they are >> taking part in "an experiment. . . . I >> have never felt that it was appropriate >> to jump on a bandwagon, whole hog, when a >> new drug comes out," she said, "unless >> it's a syndrome for which there are no >> other options. You simply don't know what >> the rare lethal or sublethal clinical >> side effect is going to be." >> >> © Copyright 1999 The Washington Post >> Company >> >> Back to the top >> >> [Navigation Bar] >> [Navigation Bar] >> >> [American Osteopathic Association][Live Online - Price Waterhouse Coopers] >> > >-- > >*************************************************************** >Karin Schumacher >Vaccine Information & Awareness (VIA) >12799 La Tortola >San Diego, CA 92129 >619-484-3197 (phone/voicemail) >619-484-1187 (fax) >via@access1.net (email) >http://www.909shot.com (NVIC website) >http://www.access1.net/via (VIA website) >*************************************************************** >We Must Have The Freedom To Choose & Respect Everyone's Choice >*************************************************************** >Any information obtained here is not to be construed as medical >OR legal advice. 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