title: Signal detection on spontaneous reports of adverse events following immunisation: a comparison of the performance of a disproportionality-based algorithm and a time-to-onset-based algorithm.
abstract: OBJECTIVE
  Disproportionality methods measure how unexpected the observed number of adverse events is. Time-to-onset (TTO) methods measure how unexpected the TTO distribution of a vaccine-event pair is compared with what is expected from other vaccines and events. Our purpose is to compare the performance associated with each method.
  
  
  METHODS
  For the disproportionality algorithms, we defined 336 combinations of stratification factors (sex, age, region and year) and threshold values of the multi-item gamma Poisson shrinker (MGPS). For the TTO algorithms, we defined 18 combinations of significance level and time windows. We used spontaneous reports of adverse events recorded for eight vaccines. The vaccine product labels were used as proxies for true safety signals. Algorithms were ranked according to their positive predictive value (PPV) for each vaccine separately; amedian rank was attributed to each algorithm across vaccines.
  
  
  RESULTS
  The algorithm with the highest median rank was based on TTO with a significance level of 0.01 and a time window of 60 days after immunisation. It had an overall PPV 2.5 times higher than for the highest-ranked MGPS algorithm, 16(th) rank overall, which was fully stratified and had a threshold value of 0.8. A TTO algorithm with roughly the same sensitivity as the highest-ranked MGPS had better specificity but longer time-to-detection.
  
  
  CONCLUSIONS
  Within the scope of this study, the majority of the TTO algorithms presented a higher PPV than for any MGPS algorithm. Considering the complementarity of TTO and disproportionality methods, a signal detection strategy combining them merits further investigation. © 2013 GlaxoSmithKline. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.
authors.affiliation: Vaccine Safety Research Group (VSRG), Vaccines Clinical Safety & Pharmacovigilance (VCSP), GlaxoSmithKline Vaccines, Wavre, Belgium.
authors.forename: Lionel
authors.initials: L
authors.lastname: van Holle
authors.forename: Vincent
authors.initials: V
authors.lastname: Bauchau
mesh_terms: D000293:Adolescent; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data; D000465:Algorithms; D001499:Bayes Theorem; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D017891:Pharmacoepidemiology / Q000379:methods*; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D013997:Time Factors; D014611:Vaccination / Q000009:adverse effects*; D014612:Vaccines / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D014612:Vaccines
keywords: Kolmogorov-Smirnov; disproportionality; pharmacoepidemiology; pharmacovigilance; signal detection; time-to-onset; vaccine safety
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