title: Patterns of Off-Label Prescribing in the Pediatric Intensive Care Unit and Prioritizing Future Research.
abstract: OBJECTIVE
  To characterize off-label prescribing among US pediatric intensive care units (PICUs), determine characteristics associated with off-label use, and identify medications in highest need for additional study.
  
  
  METHODS
  Medications prescribed for ≥1% PICU patients (age < 18 years) in 2010 were identified from 39 children's hospitals. Use in a patient younger than the Food and Drug Administration (FDA)-approved age for any indication was considered off-label. Hierarchical multivariable modeling was used to identify characteristics associated with off-label use, accounting for center effects. Highest-impact drugs were defined by: 1) high off-label use (off-label use in at least 5% of the PICU cohort), 2) high risk medication, and 3) high priority status by the FDA or Best Pharmaceuticals for Children Act (BPCA).
  
  
  RESULTS
  A total of 66,896 patients received ≥1 medication of interest (n = 162) during their PICU stay. A median of 3 (interquartile range, 2-6) unique drugs per patient were used off-label. Those who received ≥1 drug off-label (85% of the cohort) had longer median PICU (2 days vs 1 day) and hospital (6 days vs 3 days) lengths of stay and higher mortality (3.6% vs 0.7%), p < 0.001. Factors independently associated with off-label drug use included: age 1 to 5 years, chronic conditions, acute organ failures, mechanical ventilation, arterial or venous catheters, dialysis, and blood products. Half of prescribed medications (n = 84) had been used off-label: 26 with significant off-label use, 30 high-risk medications, and 47 with high FDA/BPCA priority. The highest impact medications identified were: dexmedetomidine, dopamine, hydromorphone, ketamine, lorazepam, methadone, milrinone, and oxycodone.
  
  
  CONCLUSIONS
  Most PICU patients are exposed to off-label medication use, with uncertain evidence. Future medication research in this population should focus on medications with high impact potential.
authors.affiliation: Division of Critical Care, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado ; Critical Care, Children's Hospital Colorado, Aurora, Colorado ; Center for Pharmaceutical Outcomes Research, Aurora, Colorado.
authors.forename: Angela S
authors.initials: AS
authors.lastname: Czaja
authors.affiliation: Critical Care, Children's Hospital Colorado, Aurora, Colorado ; Clinical Pharmacy, Children's Hospital Colorado, Aurora, Colorado ; Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado.
authors.forename: Pamela D
authors.initials: PD
authors.lastname: Reiter
authors.affiliation: Clinical Informatics, Children's Hospital Colorado, Aurora, Colorado.
authors.forename: M Lynn
authors.initials: ML
authors.lastname: Schultz
authors.affiliation: Center for Pharmaceutical Outcomes Research, Aurora, Colorado ; Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Valuck
keywords: off label use; pediatric intensive care units; pharmacoepidemiology; research priorities; risk factors