Studies on effects of drugs on children often not published

According to a new study by researchers at Duke University Medical Center, many of the drugs that are prescribed for children may not in fact be either safe or effective for pediatric use and could require different doses than is recommended.

The researchers say drugs such as antidepressants, anti seizure medications and sedatives are covered by a congressionally mandated program titled "pediatric exclusivity".

This means that the Food and Drug Administration (FDA) may extend the period of time that a company holds exclusive marketing rights for a drug if the manufacturer conducts FDA-requested trials on its use in children.

This in essence delays the approval of equivalent generic drugs which might compete with the product.

The researchers examined how often the results of such studies were published in peer-reviewed scientific journals, which is considered to be the most effective ways to communicate information to the medical community.

They found that less than half of the pediatric exclusivity studies were published, and the likelihood of them being published was far less if the results demonstrated the drug was unsafe or ineffective in children.

Daniel K. Benjamin, M.D., Ph.D., a pediatrician at the Duke Clinical Research Institute who also holds an appointment at the FDA's Office of Pediatric Therapeutics was the study's lead investigator, and he says because children have different physiologies than adults, they often absorb drugs differently or experience different side effects.

Therefore says Benjamin, much of pediatric drug use is done 'off label', and this means children are often treated based on what has been shown to be effective in older patients, and the results can be beneficial, harmful or not effective, depending on the available information about use of the drug in children.

The pediatric exclusivity program was originally designed by the FDA to improve knowledge of how children react differently to commonly used drugs that have not been previously studied in the pediatric population.

The Duke researchers suggest that the results of these pediatric exclusivity studies are not widely disseminated beyond mandated changes to labels.

According to Benjamin between 1998 and 2004, manufacturers conducted 253 studies through the pediatric exclusivity program on drugs indicated for the treatment of conditions such as pain, diabetes, gastroesophageal reflux, seizures and psychiatric disorders.

Important labeling changes such as significant information related to dosing, safety or efficacy that differs from adults were placed on 100 drugs, yet only 37 of the studies were published in peer-reviewed journals.

The research found that such studies could result in more than one key labeling change; where there was a dosing change, only 49 percent of studies were published in peer-reviewed journals; when there was a change to safety information, only 43 percent were published, and when the drug was found to be ineffective in children, only 38 percent were published.

Although the FDA publishes label change information on its web site, Benjamin says people must know what they are looking for and where to look, in order to find it.

He concludes that though the pediatric exclusivity program has been successful in bringing about labeling changes where indicated, more efforts are needed to better inform the medical community about these changes and the studies behind them.

The study is published in the current issue of the Journal of the American Medical Association.