Off-label drug use in hospitalized children.

OBJECTIVES To describe the magnitude of off-label drug use, to identify drugs most commonly used off-label, and to identify factors associated with off-label drug use in children hospitalized in the United States. DESIGN Retrospective cohort study. SETTING Administrative database containing inpatient resource utilization data from January 1 to December 31, 2004, from 31 tertiary care pediatric hospitals in the United States. PARTICIPANTS Hospitalized patients 18 years or younger. MAIN EXPOSURES Institution and patient characteristics. MAIN OUTCOME MEASURES Off-label drug use was defined as use of a specific drug in a patient younger than the Food and Drug Administration-approved age range for any indication of that drug. RESULTS At least 1 drug was used off-label in 297 592 (78.7%) of 355 409 patients discharged during the study. Off-label use accounted for $270 275 849 (40.5%) of the total dollars spent on these medications. Medications classified as central or autonomic nervous system agents or as fluids or nutrients, or gastrointestinal tract agents were most commonly used off-label, whereas antineoplastic agents were rarely used off-label. Factors associated with off-label use in multivariate analysis were as follows: undergoing a surgical procedure, age older than 28 days, greater severity of illness, and all-cause in-hospital mortality. CONCLUSIONS Most patients hospitalized at tertiary care pediatric institutions receive at least 1 medication outside the terms of the Food and Drug Administration product license. Substantial variation in the frequency of off-label use was observed across diagnostic categories and drug classes. Despite the frequent off-label use of drugs, using an administrative database, we cannot determine which of these treatments are unsafe or ineffective and which treatments result in substantial benefit to the patient.

[1]  M. Porter,et al.  Redefining Health Care: Creating Value-based Competition on Results , 2006 .

[2]  J. Birkmeyer,et al.  Strategies for improving surgical quality--should payers reward excellence or effort? , 2006, The New England journal of medicine.

[3]  M. Rosenthal,et al.  Early experience with pay-for-performance: from concept to practice. , 2005, JAMA.

[4]  R. Gorodischer,et al.  Off label and unlicensed drugs use in paediatric cardiology , 2005, European Journal of Clinical Pharmacology.

[5]  David Wypij,et al.  Impact of a quality improvement program on care and outcomes for children with asthma. , 2005, Archives of pediatrics & adolescent medicine.

[6]  A. Tsien,et al.  Food and Drug Administration Modernization Act , 2004 .

[7]  Brian S Mittman,et al.  Creating the Evidence Base for Quality Improvement Collaboratives , 2004, Annals of Internal Medicine.

[8]  Francois S de Brantes,et al.  A middle ground on public accountability. , 2004, The New England journal of medicine.

[9]  Sharon-Lise T Normand,et al.  Physician clinical performance assessment: prospects and barriers. , 2003, JAMA.

[10]  D. Murphy,et al.  Pediatric drug labeling: improving the safety and efficacy of pediatric therapies. , 2003, JAMA.

[11]  M. Thomson,et al.  Use of unlicensed and off‐label medications in paediatric gastroenterology with a review of the commonly used formularies in the UK , 2003, Alimentary pharmacology & therapeutics.

[12]  S. Conroy,et al.  Unlicensed and off label drug use in acute lymphoblastic leukaemia and other malignancies in children. , 2003, Annals of oncology : official journal of the European Society for Medical Oncology.

[13]  M. Lapeyre-Mestre,et al.  Adverse drug reactions and off-label drug use in paediatric outpatients. , 2002, British journal of clinical pharmacology.

[14]  B. Stricker,et al.  Unlicensed and off-label drug use in a paediatric ward of a general hospital in the Netherlands , 2002, European Journal of Clinical Pharmacology.

[15]  P. Impicciatore,et al.  Off‐label use of drugs in Italy: a prospective, observational and multicentre study , 2002, Acta paediatrica.

[16]  D. Tibboel,et al.  A survey of the use of off-label and unlicensed drugs in a Dutch children's hospital. , 2001, Pediatrics.

[17]  S. Conroy,et al.  Unlicensed and off label analgesic use in paediatric pain management , 2001, Paediatric anaesthesia.

[18]  D. Tibboel,et al.  Unapproved and off-label use of drugs in a children's hospital. , 2000, The New England journal of medicine.

[19]  Maurizio Bonati,et al.  Survey of unlicensed and off label drug use in paediatric wards in European countries , 2000, BMJ : British Medical Journal.

[20]  I. Choonara,et al.  Adverse drug reactions to unlicensed and off‐label drugs on paediatric wards: a prospective study , 1999, Acta paediatrica.

[21]  I. Choonara,et al.  Unlicensed and off label drug use in paediatric wards: prospective study , 1998, BMJ.

[22]  R. Kauffman,et al.  Is the "therapeutic orphan" about to be adopted? , 1996, Pediatrics.

[23]  R. Kauffman,et al.  Guidelines for the ethical conduct of studies to evaluate drugs in pediatric populations. Committee on Drugs, American Academy of Pediatrics. , 2018, Pediatrics.

[24]  Alfred O. Berg,et al.  Clinical Guidelines And Primary Care Guidelines For The Diagnosis And Management Of Asthma , 2012 .

[25]  R. Wetzel,et al.  Midazolam-fentanyl intravenous sedation in children: case report of respiratory arrest. , 1990, Pediatrics.

[26]  National committee for the quality of health care. , 1978, Radiologic Technology.

[27]  H. Shirkey Therapeutic orphans. , 1968, The Journal of pediatrics.