Journal calls for new system to monitor post-marketing drug safety
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《英国医生杂志》
The editors of JAMA have called for a "major restructuring" of the way that US drug regulators respond to concerns over the safety of drugs after they go on the market.
The call comes after a group of doctors uncovered delays in issuing warnings about the cholesterol lowering drug cerivastatin despite the fact that the manufacturer, Bayer, had evidence of its adverse effects for more than 18 months.
The doctors?review study and the accompanying article by the editors of JAMA have been published online ahead of the print publication because of their relevance to the current debate over drug safety (http://jama.ama-assn.org/). The JAMA editors argue that cerivastatin should have been withdrawn from the market earlier than 2001 because problems with rhabdomyolysis had been known to Bayer for some time.
According to the review study, the company had documented evidence of serious adverse effects related to cerivastatin months after the drug was launched in 1998. In addition, Bayer抯 own analyses showed that cerivastatin substantially increased the risk of rhabdomyolysis, but this information was apparently not published or disseminated to doctors or patients.
Dr Bruce Psaty from the University of Washington, Seattle, and colleagues conducted a search of the published medical literature and reviewed internal company documents that have become public during court cases where Bayer has been sued by patients allegedly harmed by the drug.
"Soon after marketing of cerivastatin, spontaneous reports identified cases of rhabdomyolysis, an uncommon condition in which the breakdown of skeletal muscle cell causes pain, weakness, and in some cases, renal failure and death," the authors wrote. Many of these cases occurred in users of cerivastatin who also took gemfibrozil, a fibrate that is used to help lower cholesterol.
The authors found that published literature showed that cerivastatin was associated with much larger risks of rhabdomyolysis than other statins. In addition, internal company documents of multiple case reports suggested an interaction with gemfibrozil within about 100 days of the launch of cerivastatin. However, the company did not add a contraindication about the concomitant use of cerivastatin and gemfibrozil to the package insert for more than 18 months.
"Despite limited data, the asymmetry between the information available to the company and the information available to patients and physicians seems striking," the authors wrote.
In the accompanying editorial, Catherine DeAngelis, JAMA抯 editor in chief, and two of the journal抯 senior editors point to "shortcomings and failures of the current imperfect system" for detecting drug safety problems after drugs go on the market. They argue that the current structure—which primarily relies on companies reporting "adverse events" and other evidence of potential problems to the Food and Drug Administration—creates conflicts of interest because drug companies "are largely responsible" for discovering and reporting problems.
The editors propose a new system that uncouples drug approval from post-marketing safety surveillance and adds new oversight requirements.
Bayer has rejected the charge and called the article抯 premise "demonstrably untrue." The company also pointed to potential conflicts of interest of the study抯 four authors. The authors, all professors at university medical schools, have served as consultants to plaintiff attorneys in Bayer litigation, and they reviewed Bayer documents initially in that capacity, Bayer said.(New York Scott Gottlieb)
The call comes after a group of doctors uncovered delays in issuing warnings about the cholesterol lowering drug cerivastatin despite the fact that the manufacturer, Bayer, had evidence of its adverse effects for more than 18 months.
The doctors?review study and the accompanying article by the editors of JAMA have been published online ahead of the print publication because of their relevance to the current debate over drug safety (http://jama.ama-assn.org/). The JAMA editors argue that cerivastatin should have been withdrawn from the market earlier than 2001 because problems with rhabdomyolysis had been known to Bayer for some time.
According to the review study, the company had documented evidence of serious adverse effects related to cerivastatin months after the drug was launched in 1998. In addition, Bayer抯 own analyses showed that cerivastatin substantially increased the risk of rhabdomyolysis, but this information was apparently not published or disseminated to doctors or patients.
Dr Bruce Psaty from the University of Washington, Seattle, and colleagues conducted a search of the published medical literature and reviewed internal company documents that have become public during court cases where Bayer has been sued by patients allegedly harmed by the drug.
"Soon after marketing of cerivastatin, spontaneous reports identified cases of rhabdomyolysis, an uncommon condition in which the breakdown of skeletal muscle cell causes pain, weakness, and in some cases, renal failure and death," the authors wrote. Many of these cases occurred in users of cerivastatin who also took gemfibrozil, a fibrate that is used to help lower cholesterol.
The authors found that published literature showed that cerivastatin was associated with much larger risks of rhabdomyolysis than other statins. In addition, internal company documents of multiple case reports suggested an interaction with gemfibrozil within about 100 days of the launch of cerivastatin. However, the company did not add a contraindication about the concomitant use of cerivastatin and gemfibrozil to the package insert for more than 18 months.
"Despite limited data, the asymmetry between the information available to the company and the information available to patients and physicians seems striking," the authors wrote.
In the accompanying editorial, Catherine DeAngelis, JAMA抯 editor in chief, and two of the journal抯 senior editors point to "shortcomings and failures of the current imperfect system" for detecting drug safety problems after drugs go on the market. They argue that the current structure—which primarily relies on companies reporting "adverse events" and other evidence of potential problems to the Food and Drug Administration—creates conflicts of interest because drug companies "are largely responsible" for discovering and reporting problems.
The editors propose a new system that uncouples drug approval from post-marketing safety surveillance and adds new oversight requirements.
Bayer has rejected the charge and called the article抯 premise "demonstrably untrue." The company also pointed to potential conflicts of interest of the study抯 four authors. The authors, all professors at university medical schools, have served as consultants to plaintiff attorneys in Bayer litigation, and they reviewed Bayer documents initially in that capacity, Bayer said.(New York Scott Gottlieb)