Off-Label Pediatric Drug Prescribing: AAP Updates Guidance

Diedtra Henderson

February 24, 2014

Because more than half of the medications approved for marketing by the US Food and Drug Administration (FDA) lack evidence of safe and effective use in pediatric patients, the practice of medicine will "more than likely" require that practitioners prescribe medicines off-label to appropriately treat pediatric patients, according to the American Academy of Pediatrics (AAP).

The group published an updated policy statement on the topic online February 24 in Pediatrics.

The AAP last issued a statement on off-label use of prescription medicines in 2002 and reaffirmed it in 2005. Since then, more than 500 medicine label revisions have been made by the FDA to reflect information about use in pediatric patients, a trend accelerated by passage of the Best Pharmaceuticals for Children Act (BPCA) and the Pediatric Research Equity Act (PREA). Acting as complementary federal sticks and carrots, the PREA mandates that almost all new medicines be studied in children if pediatric use of the product is likely, whereas the BPCA opens the door for an additional 6 months of market exclusivity for sponsors that submit completed pediatric studies to the FDA.

Still, the number of pediatric-tested remedies is exceeded by the number of FDA-approved prescription medicines that have not specifically been tested for safe and efficacious use in pediatric patients.

The AAP statement indicates that clinicians' decision making in this instance "should always be guided by the best available evidence and the importance of the benefit for the individual patient. Practitioners are in agreement regarding the importance of practicing evidence-based medicine. However, for the pediatric population, gold standard clinical trials are often not available, so practitioners must rely on either less definitive information, such as expert opinion for the age group that they are treating, or use evidence from a different population to guide practice."

The FDA does not regulate the practice of medicine, according to the statement. "The administration of an approved drug for a use that is not approved by the FDA is not considered research and does not warrant special consent or review if it is deemed to be in the individual patient’s best interest," the policy statement explains.

"To conform to accepted professional standards, the off-label use of a drug should be done in good faith, in the best interest of the patient, and without fraudulent intent," according to Kathleen A. Neville, MD, from the AAP Committee on Drugs, and coauthors.

According to the statement,

  • clinicians are responsible for deciding which medicine at which dose the pediatric patient will receive for which purpose;

  • pediatricians should continue to advocate for incentives and requirements that promote the study of medicines in children;

  • physician researchers should conduct well-designed pediatric drug studies or collaborate in them;

  • journals should publish studies about well-designed trials, irrespective of the results; and

  • institutions and payers should not settle for label revisions as the sole determinant of which medicines to include in formularies.

The statement draws a distinction between individual clinician decision making on the behalf of individual patients and the active promotion of off-label use that is prohibited, whether by the sponsor or by the clinician speaking on behalf of the sponsor.

Truly investigational off-label prescriptions should be done in the context of a well-designed clinical trial, the statement indicates. Patients and their legal guardians should be duly informed, and clinicians should document consent to proceed. In addition, because off-label prescriptions can heighten liability risks for practitioners, the statement counsels clinicians to document their decision-making process in the patient's record.

"Off-label drug use remains an important public health issue, especially for infants, young children, and children with rare diseases," Dr. Neville and the AAP committee coauthors conclude. "Evidence, not label indication, remains the gold standard from which practitioners should draw when making therapeutic decisions for their patients."

The study authors have disclosed no relevant financial relationships.

Pediatrics. Published online February 24, 2014.


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