title: Performance of Stratified and Subgrouped Disproportionality Analyses in Spontaneous Databases.
abstract: BACKGROUND
  Disproportionality analyses are used in many organisations to identify adverse drug reactions (ADRs) from spontaneous report data. Reporting patterns vary over time, with patient demographics, and between different geographical regions, and therefore subgroup analyses or adjustment by stratification may be beneficial.
  
  
  OBJECTIVE
  The objective of this study was to evaluate the performance of subgroup and stratified disproportionality analyses for a number of key covariates within spontaneous report databases of differing sizes and characteristics.
  
  
  METHODS
  Using a reference set of established ADRs, signal detection performance (sensitivity and precision) was compared for stratified, subgroup and crude (unadjusted) analyses within five spontaneous report databases (two company, one national and two international databases). Analyses were repeated for a range of covariates: age, sex, country/region of origin, calendar time period, event seriousness, vaccine/non-vaccine, reporter qualification and report source.
  
  
  RESULTS
  Subgroup analyses consistently performed better than stratified analyses in all databases. Subgroup analyses also showed benefits in both sensitivity and precision over crude analyses for the larger international databases, whilst for the smaller databases a gain in precision tended to result in some loss of sensitivity. Additionally, stratified analyses did not increase sensitivity or precision beyond that associated with analytical artefacts of the analysis. The most promising subgroup covariates were age and region/country of origin, although this varied between databases.
  
  
  CONCLUSIONS
  Subgroup analyses perform better than stratified analyses and should be considered over the latter in routine first-pass signal detection. Subgroup analyses are also clearly beneficial over crude analyses for larger databases, but further validation is required for smaller databases.
authors.affiliation: UK Medicines and Healthcare Products Regulatory Agency (MHRA), 151 Buckingham Palace Road, London, SW1W 9SZ, UK. suzie.seabroke@mhra.gsi.gov.uk.
authors.forename: Suzie
authors.initials: S
authors.lastname: Seabroke
authors.affiliation: European Medicines Agency, London, UK.
authors.forename: Gianmario
authors.initials: G
authors.lastname: Candore
authors.affiliation: Uppsala Monitoring Centre, Uppsala, Sweden.
authors.forename: Kristina
authors.initials: K
authors.lastname: Juhlin
authors.affiliation: GlaxoSmithKline, London, UK.
authors.forename: Naashika
authors.initials: N
authors.lastname: Quarcoo
authors.affiliation: AstraZeneca, Alderley Park, UK.
authors.forename: Antoni
authors.initials: A
authors.lastname: Wisniewski
authors.affiliation: AstraZeneca, Alderley Park, UK.
authors.forename: Ramin
authors.initials: R
authors.lastname: Arani
authors.affiliation: GlaxoSmithKline, London, UK.
authors.forename: Jeffery
authors.initials: J
authors.lastname: Painter
authors.affiliation: UK Medicines and Healthcare Products Regulatory Agency (MHRA), 151 Buckingham Palace Road, London, SW1W 9SZ, UK.
authors.forename: Philip
authors.initials: P
authors.lastname: Tregunno
authors.affiliation: Uppsala Monitoring Centre, Uppsala, Sweden.
authors.forename: G Niklas
authors.initials: GN
authors.lastname: Norén
authors.affiliation: European Medicines Agency, London, UK.
authors.forename: Jim
authors.initials: J
authors.lastname: Slattery
mesh_terms: D000293:Adolescent; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D002648:Child; D002675:Child, Preschool; D062313:Databases, Pharmaceutical; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D055815:Young Adult