title: Key elements in adverse drug interaction safety signals: an assessment of individual case safety reports.
abstract: BACKGROUND
  A large proportion of potential drug interactions are known from pre-authorization studies, but adverse drug reactions (ADRs) due to interactions (adverse drug interactions) are often first detected through astute observation in clinical practice. Individual case safety reports (ICSRs) are collected from broad patient populations and allow for the identification of groups of similar reports. Systematic screening for adverse drug interactions in ICSRs will require an understanding of which information on these reports can be suggestive of adverse drug interactions.
  
  
  OBJECTIVE
  The aim of the study was to identify what reported information may support the identification of drug interaction safety signals in collections of ICSRs.
  
  
  METHODS
  Three previously published safety signals of suspected adverse drug interactions were re-evaluated. To this end, 137 reports related to these signals were retrieved from the WHO Global ICSR Database, VigiBase™, and corresponding original reports were obtained from national pharmacovigilance centres. Criteria from an operational score for causality analysis of drug interactions of clinical cases, the Drug Interaction Probability Scale (DIPS), were applied to each of these reports with the aim of identifying what supportive information tends to be available in ICSRs. For three DIPS elements (plausible time course, resolution of the ADR after terminating the drug inducing the interaction without changes in affected drug therapy (positive dechallenge) and alternative causes of the reaction) we also compared the amount of information in VigiBase™ and in original reports, and in free text and structured data.
  
  
  RESULTS
  Commonly fulfilled DIPS elements on reports supporting an adverse drug interaction signal were plausible time course (50 reports; 36%) and positive dechallenge (8 reports; 6%). Alternative causes for the observed adverse reaction were observed in 72 (53%) reports. We found limited differences between VigiBase™ and original reports for the structured data, although a substantial amount of additional information was available in free text in original reports.
  
  
  CONCLUSIONS
  Information on plausible time courses and resolution of the adverse reaction upon withdrawal of the drug suspected to have induced the interaction may be a useful element in identifying suspected adverse drug interactions from ICSRs. Of these, plausible time course is by far the most commonly reported element in the three signals studied here. Our analysis also demonstrated the importance of sharing and analysing information available in free text where relevant clinical details are often available, such as those mentioned above, along with severity and dosage changes.
authors: Uppsala Monitoring Centre, WHO Collaborating Centre for International Drug Monitoring, Box 1051, SE-751-40, Uppsala, Sweden. Johanna.Strandell@who-umc.org
authors: Johanna
authors: J
authors: Strandell
authors: G Niklas
authors: GN
authors: Norén
authors: Staffan
authors: S
authors: Hägg
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data*; D016208:Databases, Factual / Q000706:statistics & numerical data; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D012720:Severity of Illness Index; D013997:Time Factors