Chani Traube, MD, FAAP, FCCM
Pediatric Intensivist, Clinical Researcher
NewYork Presbyterian Hospital
New York, New York, United States
Disclosure information not submitted.
Andzelika Dechnik, MD
Pediatric Resident
Boston Children's Hospital and Boston Medical Center
Boston, Massachusetts
Disclosure information not submitted.
Allison Schachter, BS
Medical Student
Albert Einstein College of Medicine, United States
Disclosure information not submitted.
Elizabeth Mauer, MS
Research Biostatistician
Weill Cornell Medical College, United States
Disclosure information not submitted.
Yuqing Qiu, MS
Research Biostatistician
Weill Cornell Medical College, United States
Disclosure information not submitted.
Linda Gerber, PhD
Director of the Biostatistics and Research Methodology Core and Professor of Public Health
Weil Cornell Medical College, United States
Disclosure information not submitted.
Elena Mendez-Rico, Pharm.D.
Clinical Pharmacy Manager
NY Presbyterian Hospital, United States
Disclosure information not submitted.
Title: Off Label Drug Use in Pediatric Intensive Care Units
Introduction: Studies show that >35% of critically ill adults are prescribed drugs for indications not approved by the Federal Drug Administration; this off-label use is associated with an increased rate of serious adverse events. There are no large-scale studies describing frequency of off-label drug use in critically ill children. We hypothesized that >50% of PICU patients are exposed to off-label drugs, with greater use in the youngest and sickest children. We further hypothesized that off-label drug use is associated with hospital mortality.
Methods: Retrospective cohort study including all children 0-18 years old admitted to 25 PICUs in the US over a 4-month period in 2017, utilizing the Pediatric Health Information Systems database. Off-label drug use was defined as administration of a drug without a labeled indication, as recorded in Micromedex Solutions. Bivariate association tests were used to describe relationships between patient characteristics, receipt of off-label drugs, and ICU mortality. All variables that achieved significance were built into a mixed-effect logistic regression model, adjusted for ICU site.
Results: 31,886 children and 177,286 PICU days were included. 87% of children received at least one off-label drug, with a median exposure of 3 off-label drugs (IQR 1-8) per PICU patient. In multivariable analysis, patients most likely to receive 3 or more off-label drugs were younger (< age 13), Caucasian, mechanically ventilated, with higher severity of illness, and longer ICU stay. After controlling for patient’s risk of mortality, receipt of off-label drugs was independently associated with excess mortality, with a dose-response effect noted for 1-2 off-label drugs (aOR 2.3, p=0.016), and for 3 or more (aOR 4.2, p< 0.001).
Conclusions: The majority of critically ill children are prescribed off-label drugs during their PICU stay, with increased exposure in the youngest and sickest children. Although we make no causal inference in this retrospective study, off-label use was independently associated with excess ICU mortality in this cohort. Prospective multi-center research is needed to detect serious adverse events related to off-label drug use in the PICU, and it would be prudent for the FDA to create economic incentives for pharmaceutical companies to test drugs in critically ill children.