title: Assessment of off-label use of denosumab 60 mg injection during the early postmarketing period using health insurance claims data.
abstract: Off-label use of denosumab 60 milligram (mg) injection was assessed within an administrative claims database. The completeness of claims to assess off-label use was investigated with medical record review. Potential denosumab 60 mg off-label use was observed based on claims, but many had evidence of on-label indications based on medical record review.
  
  
  BACKGROUND
  Denosumab 60 mg injection is approved in the USA to treat patients at high fracture risk due to postmenopausal osteoporosis, male osteoporosis, and hormone therapy for the treatment of prostate and breast cancers. Its RANK ligand-inhibiting effect makes it a candidate for the off-label treatment of other conditions mediated by the rate of bone resorption by osteoclasts. To better understand its utilization patterns, we assessed off-label use of denosumab 60 mg within an administrative claims database.
  
  
  METHODS
  Definite, probable, and possible denosumab 60 mg users were identified during the early postmarketing period within a claims database of a US healthcare insurer. Medical record review confirmed a sample of these users. Off-label use among definite and probable users and all chart-confirmed users was classified using claims-derived age, dose interval, and diagnosis and treatment received relative to the administration date. Among chart-confirmed users classified as off-label, patient characteristics related to treatment indication were abstracted from medical records to investigate the completeness of claims to study off-label medication use.
  
  
  RESULTS
  Off-label use was identified based on claims in approximately 25 % of definite and probable denosumab 60 mg users and 35 % of chart-confirmed users. Medical record review identified evidence of on-label indications in 81 % of chart-confirmed users classified as off-label in claims.
  
  
  CONCLUSIONS
  Many of the off-label denosumab 60 mg users had diagnoses or treatment consistent with on-label indications based on medical record review, suggesting these are under-recorded in claims data. It is warranted to be cautious when using administrative databases to assess off-label medication use.
authors.affiliation: Epidemiology, Optum , Ann Arbor, MI, USA. veena.hoffman@optum.com.
authors.forename: V
authors.initials: V
authors.lastname: Hoffman
authors.affiliation: Center for Observational Research, Amgen Inc., Thousand Oaks, CA, USA.
authors.forename: F
authors.initials: F
authors.lastname: Xue
authors.affiliation: Epidemiology, Optum , Waltham, MA, USA.
authors.forename: B
authors.initials: B
authors.lastname: Gardstein
authors.affiliation: Epidemiology, Optum , Waltham, MA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Skerry
authors.affiliation: Center for Observational Research, Amgen Inc., Thousand Oaks, CA, USA.
authors.forename: C W
authors.initials: CW
authors.lastname: Critchlow
authors.affiliation: Epidemiology, Optum , Ann Arbor, MI, USA.
authors.forename: C
authors.initials: C
authors.lastname: Enger
mesh_terms: D000293:Adolescent; D000465:Algorithms; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D016208:Databases, Factual; D000069448:Denosumab / Q000008:administration & dosage* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004363:Drug Utilization / Q000706:statistics & numerical data; D017723:Drug Utilization Review / Q000379:methods; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D007348:Insurance, Health / Q000706:statistics & numerical data; D008297:Male; D056687:Off-Label Use / Q000706:statistics & numerical data*; D010024:Osteoporosis / Q000188:drug therapy; D011358:Product Surveillance, Postmarketing; D014481:United States
chemical_list: D050071:Bone Density Conservation Agents; D000069448:Denosumab
keywords: Denosumab 60 mg; Health insurance claims data; Off-label; Utilization