title: Diagnostic E-codes for commonly used, narrow therapeutic index medications poorly predict adverse drug events.
abstract: OBJECTIVE
  We sought to examine the validity of specific hospital discharge codes in identifying drug toxicity precipitating hospitalization, among elderly users of high-risk medications.
  
  
  METHODS
  We conducted a cross-sectional evaluation assessing the diagnostic test characteristics of International Classification of Diseases-9 External-Cause-of-Injury codes (E-codes) compared with a reference standard of medical record review. This study was nested within a prospective cohort of elders using warfarin, digoxin, or phenytoin as identified in the Pharmaceutical Assistance Contract for the Elderly benefit program.
  
  
  RESULTS
  We identified 4,803 subjects contributing 11,409 person-years of exposure to at least one of three drug groups. Subjects experienced 8,756 hospitalizations, of which 304 were deemed, by expert review, to be a result of an adverse event of warfarin, digoxin, or phenytoin. The sensitivity, specificity, and positive (PPVs) and negative predictive values for drug-specific E-codes were warfarin--25.5%, 98.3%, 46.6%, and 95.7%; digoxin--84.0%, 99.1%, 56.8%, and 99.8%; and phenytoin--86.7%, 98.7%, 59.1%, and 99.7%.
  
  
  CONCLUSIONS
  E-codes for digoxin and phenytoin have a high sensitivity, but E-codes for all three medications have poor PPVs, a result that might produce misclassification in studies based solely on discharge coding. Investigators should confirm such rare events via medical record review.
authors.affiliation: Center for Clinical Epidemiology & Biostatistics, Department of Biostatistics & Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6021, USA. celeonar@mail.med.upenn.edu
authors.forename: Charles E
authors.initials: CE
authors.lastname: Leonard
authors.forename: Kevin
authors.initials: K
authors.lastname: Haynes
authors.forename: A Russell
authors.initials: AR
authors.lastname: Localio
authors.forename: Sean
authors.initials: S
authors.lastname: Hennessy
authors.forename: Jennifer
authors.initials: J
authors.lastname: Tjia
authors.forename: Abigail
authors.initials: A
authors.lastname: Cohen
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Kimmel
authors.forename: Harold I
authors.initials: HI
authors.lastname: Feldman
authors.forename: Joshua P
authors.initials: JP
authors.lastname: Metlay
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems / Q000592:standards*; D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects; D000925:Anticoagulants / Q000009:adverse effects; D000927:Anticonvulsants / Q000009:adverse effects; D003430:Cross-Sectional Studies; D004077:Digoxin / Q000009:adverse effects; D064420:Drug-Related Side Effects and Adverse Reactions; D005568:Forms and Records Control / Q000592:standards; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D038801:International Classification of Diseases; D008499:Medical Records / Q000592:standards*; D010351:Patient Discharge; D010414:Pennsylvania; D010672:Phenytoin / Q000009:adverse effects; D014859:Warfarin / Q000009:adverse effects
chemical_list: D000889:Anti-Arrhythmia Agents; D000925:Anticoagulants; D000927:Anticonvulsants; D014859:Warfarin; D010672:Phenytoin; D004077:Digoxin