Analysis: Off-Label Use Common in Kids

By STEVE MITCHELL

Nearly 80 percent of hospitalized children receive drugs that have been approved only for adults, according to the largest-ever study to look at off-label use in the pediatric setting.

The researchers who conducted the study are urging both the pharmaceutical industry and the Food and Drug Administration to play a role in addressing the findings, which appear in the March issue of the Archives of Pediatrics and Adolescent Medicine.

We need to do more, lead author Samir Shah, a pediatrician specializing in infectious diseases at The Children’s Hospital of Philadelphia, told United Press International.

When almost 80 percent of patients receive a drug off-label, that’s a situation that is unacceptable, added Shah, who also serves as senior scholar at the center for clinical epidemiology and biostatistics at the University of Pennsylvania.

The trend of off-label use in the pediatric setting may even be higher than the study findings suggest, because the researchers only considered age and did not include other off-label uses, such as for unapproved diseases or other indications.

Our study really underestimated the magnitude of off-label drug use because all we looked at was age, not indication, Shah said.

The main concern is that since these drugs have not been formally studied in children, the risks and benefits in this patient population are unknown.

This is a pretty big issue, Shah said. These are sick children we’re talking about, and we probably need to look into those issues more closely.

Although the findings don’t reveal whether the off-label use is having a negative impact on patients, they do show that there is a significant financial toll.

The expenditure of the off-label use amounted to $270 million, or 40 percent of the total dollars spent on children’s medication in the study.

This has huge, huge financial implications, Shah said.

One measure that would help is mandating postmarketing surveillance, he said. This would help uncover situations where off-label use is beneficial and where it jeopardizes patient safety or is economically wasteful.

He noted that the heart problems associated with Vioxx and the suicidality related to anti-depressants were uncovered largely as a result of postmarketing surveillance.

Drug companies can play a role and the FDA can create situations to facilitate that process, he said.

Shah said he would like it to be mandatory that a formalized postmarketing surveillance program is put into place any time a new drug is launched. There should also be a requirement that the companies report back to the FDA after a period of time to detail the problems they’ve identified with a particular drug.

This would help keep physicians and patients aware of the potential risks of drugs and enable safer and more effective use of them, he said.

The FDA said it was aware of the off-label use of drugs in children and has been working to address the issue.

The FDA and the American Academy of Pediatrics have been aware for decades that products used in children often have not been studied in them and have advocated for decades that sponsors need to study their product in the pediatric population, the agency said in a statement to UPI. We have made progress, but we agree there is still much to be done.

The FDA added that 118 drugs have now been approved for use in children and adolescents, and it is working with the National Institutes of Health to get pediatric studies done for older drugs.

We share the concerns of the authors, Ken Johnson, Pharmaceutical Research and Manufacturers of America senior vice president, told UPI. While PhRMA believes that a significant amount of pediatric-use information exists for recently approved drugs, some of the medicines with expired patents may be extensively used off-label in pediatric patients, and updating the drug label for these products is important.

Johnson, who noted the study applied mainly to older and generic medicines, said the findings could help determine which drugs need pediatric testing.

A panel of pediatricians ought to be convened to review the medical and scientific literature relating to pediatric use of these medicines, he added.

In the study, Shah and colleagues examined information from 2004 from the Pediatric Health Information Systems database, which contains patient records from 31 major U.S. children’s hospitals. They focused on 90 drugs that are administered frequently to children or were recommended for further pediatric study by the FDA.

Of the 355,000 children treated in the hospitals in 2004, almost 300,000, or 79 percent, received at least one drug off-label. The drugs most likely to be used off-label included central or autonomic nervous system agents, nutrients and gastrointestinal agents.

Anti-cancer agents were the least likely to be used off-label.

Children who were more likely to receive drugs off-label included those who underwent surgery, were older than 28 days or had more severe illnesses. In addition, children who died in the hospital were more likely to receive drugs off-label. But rather than indicating unsafe use of a drug, this could merely represent a last-ditch effort after all other options had been exhausted, Shah said.