Disagreements on Doses

November 30, 2006

Hundreds of drugs that have been prescribed for children may not be safe or effective for pediatric use or may require different doses than currently suggested, but some of this information may not be reaching the medical community. The drugs include antidepressants, anti-seizure medications, and sedatives.

Disagreements on Doses

 David Waldorf

Researchers at Duke Medical Center examined drugs covered by a congressionally mandated program known as "pediatric exclusivity." Under the program, the Food and Drug Administration (FDA) may extend the period that gives a company exclusive marketing rights for a drug—thereby delaying the sale of competing generic drugs—if the manufacturer conducts FDA-requested trials on its use in children. The manufacturer is not required to publish the results of the study.

The Duke researchers looked at how often the results of such studies were published in peer-reviewed scientific journals, often cited as among the most effective ways to communicate information to the medical community. The team reported its findings in the Journal of the American Medical Association.

Between 1998 and 2004, drug manufacturers conducted 253 studies under the pediatric-exclusivity program. According to Daniel K. Benjamin, a pediatrician at the Duke Clinical Research Institute who also holds an appointment in the FDA's Office of Pediatric Therapeutics, the studies resulted in key labeling changes—defined as a significant finding related to dosing, safety, or efficacy for children—on 100 drugs. But of those studies, only thirty-seven were published in peer-reviewed journals, the researchers found.

If a study resulted in a "positive" labeling change, meaning that a drug's safety and effectiveness in children was established, it was more likely to be published. Fifty-four percent of such studies were published, compared with 36 percent of studies that resulted in a negative labeling change. The latter might include a finding that the drug showed no meaningful clinical effect in children or that it was associated with a worse outcome than the comparison therapy.

Though the pediatric-exclusivity program itself has been a useful tool in making drugs safer for children through labeling changes, more can be done to ensure that this information gets into the right hands, says Benjamin. The FDA publishes label change information on its website, but users must know what they are looking for and where to look in order to find it, he says.

"Physicians are used to using peer-reviewed journals as a source for the latest medical information, so it makes sense to get this information in there."