Most Children In US Hospitals Receive Medicines Off-label

"We measured the magnitude of off-label use of drugs in children," said study leader Samir S. Shah, M.D., a pediatrician specializing in infectious diseases at The Children's Hospital of Philadelphia. "Given the nature of the available data, we could not evaluate safety and effectiveness of those medications, although those are important concerns. However, only a small number of drugs have been formally tested in children."

Once the U.S. Food and Drug Administration (FDA) approves a drug for any indicated use, physicians may legally prescribe the drug for different conditions and for patients in other age groups. This study measured off-label use only as defined by age, not by indicated conditions.

"With nearly 80 percent of children receiving off-label medications during hospitalizations, we need to focus our attention on the process by which medications are approved for pediatrics," said senior author Anthony D. Slonim, M.D., Dr.P.H., Executive Director of the Center for Clinical Effectiveness at Children's National Medical Center. "It is imperative that we thoroughly review this process to ensure that children are being treated with the safest, most effective therapies."

Researchers in the Pediatric Health Information Systems Research Group, representing various medical centers, analyzed patient records from 31 major U.S. children's hospitals for the entire year of 2004. At least one drug was used off-label in 79 percent of the more than 355,000 children requiring hospitalization. Off-label use accounted for $270 million, some 40 percent, of the total dollars spent on children's medication in the study, which appears in the March issue of the Archives of Pediatrics and Adolescent Medicine.

Off-label prescribing is relatively common among adult patients as well, but it has long been recognized that a large proportion of drugs used in pediatrics have never been tested in children. Over the past decade, federal regulations providing financial incentives to pharmaceutical companies have helped increase the number of drugs tested and approved for children. However, said Dr. Shah, "there was little information on the extent of off-label use among children, the types of drugs used off-label, and the characteristics of hospitalized children receiving those drugs."

All previous studies of off-label drug use in hospitalized children were performed outside the United States, often limited to specific conditions or to patients in single medical centers. This current study focused on 90 drugs that were either administered frequently to children or were recommended for further pediatric study by the FDA.

The drugs most likely to be used off-label in children were those approved for use on the central nervous system or autonomic nervous system, in addition to nutrients and gastrointestinal agents. For instance, 28 percent of the patients in the database received morphine, although the FDA has not approved it for use in children. Anti-cancer drugs were the least likely to be used off-label, possibly because such drugs are more likely to have been tested in pediatric cancer patients, who frequently participate in clinical trials.

Children were more likely to receive drugs off-label if they underwent surgery, were older than 28 days and had more severe illnesses. "Critically ill children may have failed to respond to conventional therapies and may receive drugs off-label because they have no approved options," said Dr. Shah.

The authors point out that, while physicians may sometimes have no alternatives to treating children with off-label medications, the practice is not risk-free. "Using drugs that have been insufficiently studied in children has contributed to adverse outcomes, which have been documented in the medical literature," said Dr. Shah. "We hope that by better defining the magnitude of off-label drug use, our study may help encourage greater cooperation among industry, academia and government in carrying out studies to better protect children."

In addition to his position at The Children's Hospital of Philadelphia, Dr. Shah is a Senior Scholar at the Center for Clinical Epidemiology and Biostatistics at the University of Pennsylvania School of Medicine. Dr. Shah and Dr. Slonim's co-authors, from several other universities and medical centers, were Matthew Hall, Ph.D.; Denise M. Goodman, M.D., M.S.; Pamela Feuer, M.D.; Vidya Sharma, M.B.B.S., M.P.H.; Crayton Fargason, Jr., M.D.; Daniel Hyman, M.D., M.M.M.; Kathy Jenkins, M.D., M.P.H.; Marjorie L. White, M.D.; Fiona H. Levy, M.D.; James E. Levin, M.D., Ph.D.; and David Bertoch, M.H.A.