title: Detecting treatment emergent adverse events in clinical trials : a comparison of spontaneously reported and solicited collection methods.
abstract: BACKGROUND
  The collection of adverse event data is an important component of clinical trials, but it is not clear whether solicited or unsolicited collection methods are better at distinguishing drug effects from the effects of placebo. The objective of this analysis is to compare the reporting rates and the ability to detect drug-placebo differences with spontaneous versus solicited adverse event collection methods.
  
  
  METHODS
  Adverse events were collected by spontaneous (unsolicited) reporting and by structured questionnaires in three randomised, double-blind clinical trials. For both spontaneous and solicited adverse event collection methods, a drug/placebo (D/P) reporting ratio was computed by dividing the reporting rate for the experimental drug by the reporting rate for placebo for each adverse event. An index (Sp-So index) was calculated by dividing the spontaneous D/P ratio by the solicited D/P ratio. A number >1.0 indicates that the spontaneous adverse event collection method is more effective in distinguishing the drug from placebo and a number <1.0 suggests that the solicited adverse event collection method is more effective in distinguishing the drug from placebo.
  
  
  RESULTS
  Reporting rates were greater when events were solicited than when the spontaneous reporting approach was used. The Sp-So index was >1.0 for 22 of the 29 (75.9%) events examined, suggesting that spontaneous collection of adverse events is more effective in distinguishing drug effect from placebo than the solicited approach. However, more statistically significant differences between drug and placebo were detected by the solicited method (nine events) than the spontaneous method (five events). This is due, in part, to the fact that differences in the percentages of adverse events between drug and placebo (rather than ratios of event rates) were more often greater when the solicited approach was used.
  
  
  CONCLUSIONS
  As expected, adverse events collected by solicitation leads to higher reporting rates. However, it is not clear that solicitation of events leads to greater ability to detect drug-placebo differences. By using a ratio to assess drug-placebo differences, spontaneous reporting provided larger drug-placebo differences more often than solicitation.
authors.affiliation: Lilly Research Laboratories, Indianapolis, Indiana 46285, USA. jfwernick@lilly.com
authors.forename: Joachim F
authors.initials: JF
authors.lastname: Wernicke
authors.forename: Douglas
authors.initials: D
authors.lastname: Faries
authors.forename: Denái
authors.initials: D
authors.lastname: Milton
authors.forename: Karen
authors.initials: K
authors.lastname: Weyrauch
mesh_terms: D000293:Adolescent; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D002648:Child; D003625:Data Collection; D004311:Double-Blind Method; D006801:Humans; D016032:Randomized Controlled Trials as Topic / Q000009:adverse effects*