According to background information in the article, "For medicines that are effective, prompt approval provides rapid access to the health benefits of new drugs. At the same time, U.S. patients are increasingly the first to receive new medications, some of which are subsequently discovered to have serious adverse effects. As a result, the challenge of early detection is increasingly borne by the U.S. postmarketing systems."
Bruce M. Psaty, M.D., Ph.D., from the University of Washington, Seattle, and colleagues conducted a search of the published medical literature and reviewed internal company documents that have become part of the public record during a trial in Nueces County, Texas. The information gathered was used to review the association between the use of cerivastatin sodium (a statin drug removed from the market in 2001) and the risk of rhabdomyolysis (a disorder involving damage to muscle tissue) to illustrate the operation and limitations of the current U.S. postmarketing safety-surveillance system.
"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 report. "Many but not all of them occurred in cerivastatin users who also took gemfibrozil (a fibrate, another type of drug used to help lower cholesterol). "In the published literature, cerivastatin was associated with much larger risks of rhabdomyolysis than other statins."... "In internal company documents, multiple case reports suggested a drug-drug interaction within approximately 100 days of the launch [of cerivastatin] in 1998; however the company did not add a contraindication [warning] about the concomitant use of cerivastatin and gemfibrozil to the package insert for more than 18 months," the authors note. "Despite limited data, the asymmetry between the information available to the company and the information available to patients and physicians seems striking."
"This history of cerivastatin illustrates a flaw in the current U.S. system for SADR (suspected adverse drug reactions) reporting and monitoring. When serious adverse effects such as rhabdomyolysis appear after marketing, defects in the safety-surveillance system can, depending in part on the response of the pharmaceutical company, pose a threat to the health of the public," the authors write. "To balance the interests of patients and industry, decisions about label changes, new studies, suspension of sales, or withdrawal of drugs might best be made by an outside group of disinterested reviewers."
"In the United States, once a drug is approved for marketing, there is no regularly scheduled re-review of the drug. In Europe, drug approvals are re-reviewed every 5 years. This process encourages companies to attend to outstanding issues, such as launching promised phase 4 trials, before the scheduled re-review, and occasionally, companies have withdrawn drugs from the market rather than participate in a re-review." The authors continue, "Europe also assesses a postmarketing fee that contributes to postmarketing safety surveillance efforts." The authors add such a system might also work in the U.S. and enhance patient safety as well.
(JAMA. 2004;292: 26220 2631. Available post-embargo at JAMA.com).
Editor's Note: Please see JAMA article for the authors' financial disclosures.
Counterpoint: Potential for Conflict of Interest in the Evaluation of Suspected Adverse Drug Reactions
In an accompanying commentary, Brian L. Strom, M.D., M.P.H., from University of Pennsylvania School of Medicine, Philadelphia, places the events surrounding cerivastatin within the context of the current system for postmarketing surveillance of medications.
"However there is indeed a conflict of interest in asking industry to monitor its own drugs. It is imperative, therefore, that the FDA continue to be bolstered, both in its efforts to monitor drug safety and in its new risk management initatives. In my opinion, there is no need for additional duplicative regulatory oversight of newly marketed drugs; our FDA colleagues can be trusted to do the job, given sufficient resources. However, it is also critical that the nation commit to adequately funding CERTs (Centers for Education and Research in Therapeutics), a Center for Drug Surveillance, or some analogous structure, to complement the regulatory mission of the FDA.
(JAMA. 2004;292:2643-2646. Available post-embargo at JAMA.com)
Editor's Note: Please see the JAMA article for the author's financial disclosures.