title: A novel signal detection algorithm for identifying hidden drug-drug interactions in adverse event reports.
abstract: OBJECTIVE
  Adverse drug events (ADEs) are common and account for 770 000 injuries and deaths each year and drug interactions account for as much as 30% of these ADEs. Spontaneous reporting systems routinely collect ADEs from patients on complex combinations of medications and provide an opportunity to discover unexpected drug interactions. Unfortunately, current algorithms for such "signal detection" are limited by underreporting of interactions that are not expected. We present a novel method to identify latent drug interaction signals in the case of underreporting.
  
  
  METHODS
  We identified eight clinically significant adverse events. We used the FDA's Adverse Event Reporting System to build profiles for these adverse events based on the side effects of drugs known to produce them. We then looked for pairs of drugs that match these single-drug profiles in order to predict potential interactions. We evaluated these interactions in two independent data sets and also through a retrospective analysis of the Stanford Hospital electronic medical records.
  
  
  RESULTS
  We identified 171 novel drug interactions (for eight adverse event categories) that are significantly enriched for known drug interactions (p=0.0009) and used the electronic medical record for independently testing drug interaction hypotheses using multivariate statistical models with covariates.
  
  
  CONCLUSIONS
  Our method provides an option for detecting hidden interactions in spontaneous reporting systems by using side effect profiles to infer the presence of unreported adverse events.
authors.affiliation: Biomedical Informatics Training Program, Stanford University, Stanford, California, USA.
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Tatonetti
authors.forename: Guy Haskin
authors.initials: GH
authors.lastname: Fernald
authors.forename: Russ B
authors.initials: RB
authors.lastname: Altman
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems; D000465:Algorithms; D004347:Drug Interactions; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis* / Q000453:epidemiology; D005189:False Positive Reactions; D006801:Humans; D016015:Logistic Models; D012372:ROC Curve; D014481:United States; D014486:United States Food and Drug Administration