Safety data from kid drug trials often unpublished

When drugs approved for adults are studied in youngsters, the research yields important safety data that could guide the use of these medications in children, a report published this week indicates.

But in most cases these studies never appear in peer-reviewed journals, and when they do, half of them don’t focus on the important new safety data that’s been generated, Dr. Daniel K. Benjamin Jr., from Duke Clinical Research Institute in Durham, North Carolina and colleagues found.

“Specifically, trials that uncover new safety findings are less likely to be published than other types of trials, and trials that uncover results unfavorable to a company (or its product) are less likely to be published than those with favorable results,” they report in the Archives of Pediatrics and Adolescent Medicine.

Prescription drugs are often administered “off-label” to children largely because many of them have only been tested in and approved for use in adults. As such, drugs are often given to children without fully knowing if they will be beneficial, harmful, or neither.

To address this problem, the US Congress passed the Food and Drug Administration (FDA) Modernization Act in 1997, which, in part, extends the exclusive marketing rights for a particular drug if the drug maker conducts FDA-requested studies of its effects in children. However, it is unclear how often the results of pediatric drug trials are published in peer-reviewed medical journals and just what information gets published.

In the first 10 years of the so-called “pediatric exclusivity” program, more than 95,000 children were enrolled in 365 pediatric trials for the 153 drugs that were granted pediatric exclusivity extensions. Overall, there were 137 pediatric labeling changes, which means that changes were made to the information the drug company gives to doctors about how the drug should be used.

Benjamin and his team reviewed 129 of the 137 labeling changes. They found that for 96 products (74 percent), no new safety information was added to the product label. For 33 products (26 percent), new pediatric safety information was added to the product label. For 12 of these products, “unexpected and important neuropsychiatric safety findings” emerged in the pediatric drug trials.

For example, in a pediatric trial of ribavirin and interferon alpha for hepatitis C infection, FDA medical reviewers found an increase in suicidal thoughts compared with adults.

Agitation was observed in young children given the stomach acid drug famotidine (marketed as Pepcid or Fluxid). Aggressive and hyperactive behavior was more often seen in children exposed to the bladder-control drug tolterodine (Detrol), and post-marketing data for the migraine drug sumatriptan showed “serious adverse events” in children, which have been only rarely seen in adults, including stroke, vision loss and death.

In addition to the 12 products with neuropsychiatric safety issues, 21 products tested in children had “other important safety findings.”

What’s concerning, the researchers say, is that less than half of the trials (16 of 33) that generated new safety issues were ever reported in a peer-reviewed medical journal.

What’s more, of the 16 trials that were published in reputable journals, 7 articles (44 percent) substantially differed in their presentation and interpretation of the data submitted to the FDA.

In an email to Reuters Health, Benjamin said: “The results investigators and pharmaceutical companies—who have a conflict of interest—emphasize in the peer-review literature are often different than what FDA reviewers report.”

“Greater access to data will result in greater dissemination of findings, and thus improve children’s health,” Benjamin and colleagues conclude in their report.

SOURCE: Archives of Pediatrics and Adolescent Medicine, December 2009.