Little Is Known of Drugs' Safety and Effectiveness in Children

    PHILADELPHIA, March 5 /PRNewswire-USNewswire/ -- Nearly four out of
five hospitalized children receive medications that have been tested and
approved only for adults, according to a study of hundreds of thousands of
patient records. This so-called "off-label" use of drugs was thought to be
especially common in children, and the new research, the largest-ever U.S.
pediatric study, confirms this.
    "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.
    About The Children's Hospital of Philadelphia: The Children's Hospital
of Philadelphia was founded in 1855 as the nation's first pediatric
hospital. Through its long-standing commitment to providing exceptional
patient care, training new generations of pediatric healthcare
professionals and pioneering major research initiatives, Children's
Hospital has fostered many discoveries that have benefited children
worldwide. Its pediatric research program is among the largest in the
country, ranking third in National Institutes of Health funding. In
addition, its unique family-centered care and public service programs have
brought the 430-bed hospital recognition as a leading advocate for children
and adolescents. For more information, visit http://www.chop.edu.
    About Children's National Medical Center: Children's National Medical
Center, located in Washington, D.C., is a proven leader in the development
of innovative new treatments for childhood illness and injury. Consistently
ranked among the top pediatric hospitals in America, Children's has been
serving the nation's children for more than 130 years. Children's Research
Institute, the academic arm of Children's National Medical Center,
encompasses the translational, clinical and community research efforts of
the institution. For more information about Children's National Medical
Center, visit http://www.dcchildrens.com.
    Contacts:
    John Ascenzi                            Emily Dammeyer
    The Children's Hospital of              Children's National Medical
    Philadelphia                            Center
    (267)426-6055                           (202)884-4500
    Ascenzi@email.chop.edu                  Edammeye@cnmc.org

SOURCE The Children's Hospital of Philadelphia