Off-label Medication Prescribing Patterns in Pediatrics: An Update

Abstract

A B S T R A C TOBJECTIVES: To describe the frequency of off-label drug use in 2014 as defined by the Food and Drug Administration (FDA)-approved age ranges in patients #18 years of age, to determine the rate of off-label drug use in 2014 by drug classification, and to compare current off-label medication usage rates with historical rates.METHODS: This is a retrospective cohort study of an administrative database containing inpatient resource use data from January 1, 2014, to December 31, 2014. Patients #18 years of age receiving 1 of 76 selected commonly prescribed medications are included. Off-label drug use is defined as use in a patient younger than the lower limit of the FDA-approved age range for any indication or dosage form of that drug. RESULTS:At least 1 drug was prescribed off label in 779 270 of 2 773 770 (28.1%) patient visits during the study period. Younger age, longer hospital stays, and mortality were associated with higher rates of off-label medication prescription. Off-label usage of certain medications differed between care settings. Rates of off-label medication use were higher in observational (45.5%), inpatient (53.9%), and ambulatory (54.2%) settings. CONCLUSIONS:Although off-label drug use at major US pediatric hospitals is declining, 1 out of every 4 medications is not in accordance with FDA label indications for patient age. There exists substantial variation in off-label drug use among drug categories and encounter types. Although many commonly prescribed medications are FDA-approved for use in subpopulations of pediatric patients, studies of their safety, efficacy, pharmacokinetics, and optimal dosing are ongoing.

Beyond the Randomized Clinical Trial: Innovative Data Science to Close the Pediatric Evidence Gap

“…Additionally, it has been shown that younger children tend to have a stronger placebo response than older children . This would make it especially difficult to demonstrate efficacy in younger children, which is problematic considering that the off‐label drug use is highest in children in the first year of life …”

“…63 This would make it especially difficult to demonstrate efficacy in younger children, which is problematic considering that the off-label drug use is highest in children in the first year of life. 11 One way to limit the impact of placebo response on trial outcomes would be to identify baseline predictors of placebo response so that trials can be enriched prerandomization with subjects that are less likely to respond strongly to placebo. 8 This strategy has been used in pediatric trials, resulting, for example, in the successful application for a pediatric indication of rizatriptan for acute…”

“…9,10 Failed drug trials-and the general lack of pediatric clinical trials being performed particularly in primary health care-contribute to the high prevalence of off-label drug use in children, especially in the first years of life. 11 It is clear that despite the advances in approaches to data collection and analysis, a large need for additional research in pediatrics still remains.…”

Navigating off‐label and unlicensed medicines use in obstetric and paediatric clinical practice

“…Prevalence of self‐medication, off‐label, is even higher, with over‐the‐counter and complementary medicines use in pregnancy ranging between 25% and 68% . In 2014, the frequency of paediatric off‐label prescribing in the US ranged from 45.5% to 54.2% . European studies in 2017 showed that between 2% and 100% of children in an outpatient setting and up to 74% of pregnant women received medicines off‐label .…”

“…6,7 In 2014, the frequency of paediatric off-label prescribing in the US ranged from 45.5% to 54.2%. 8 European studies in 2017 showed that between 2% and 100% of children in an outpatient setting and up to 74% of pregnant women received medicines off-label. 9 The Australian experience of off-label (34%-95.6%) and unlicensed (5.7%-34.6%) medicines use in neonatal intensive care varies, with 44%-100% of all neonates administered at least one such medicine during their hospital stay.…”