title: Seasonal and Geographic Variation in Adverse Event Reporting.
abstract: BACKGROUND
  Many illnesses demonstrate seasonal and geographic variations. Pharmacovigilance is unique among public health surveillance systems in terms of the clinical diversity of the events under surveillance. Since many pharmacovigilance signal detection methodologies are geared towards looking for increased frequency of spontaneous adverse drug event (ADE) reporting over variable time frames, seasonality of ADEs may have implications for signal detection.
  
  
  OBJECTIVE
  The aim of this study was to investigate whether a set of illnesses that might be expected to display seasonality in general, did so when spontaneously reported as ADEs.
  
  
  METHODS
  We performed our analysis with the publically available US FDA Adverse Event Reporting System (FAERS) data. We selected a convenience sample of events possibly triggered by seasonal factors (hypothermia, Raynaud's phenomenon, photosensitivity reaction, heat exhaustion, heat stroke, and sunburn) and events for which previous literature experience suggests seasonality (anencephaly and interstitial lung disease). Our statistical procedures can be explained in terms of a simple physicogeometric setting: the unit circle divided into 6 (semiannual sinusoidal) or 12 (annual sinusoidal) arcs. When reporting frequencies (weights) are more or less evenly distributed across months, the center of mass of the circle would not be significantly displaced from the origin (0, 0). Distinct seasonal patterns will significantly displace the center of mass of the circle.
  
  
  RESULTS
  Various patterns of seasonality were identified for some, but not all, events and region-event pairs. USA displayed the most instances of seasonality. Scandinavia did not display seasonality for any events. Seasonality was usually annual sinusoidal. Possible explanations for failure to observe seasonality are briefly considered.
  
  
  CONCLUSIONS
  Understanding seasonality of spontaneous ADE reporting may have public health policy and research implications and may mitigate false-positive and missed true-positive pharmacovigilance signals. More systematic study of seasonality of spontaneous ADE reporting, including additional events with more or less biological rationale for seasonality, is a logical extension of this analysis.
authors.affiliation: Department of Mathematics and Statistics, Villanova University, Villanova, PA, USA.
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Marrero
authors.affiliation: Pfizer Inc., New York, NY, USA. eric.hung@pfizer.com.
authors.forename: Eric Y
authors.initials: EY
authors.lastname: Hung
authors.affiliation: Pfizer Inc., New York, NY, USA.|New York University Medical Center, New York, NY, USA.
authors.forename: Manfred
authors.initials: M
authors.lastname: Hauben