title: Sources of information used by regulatory agencies on the generation of drug safety alerts.
abstract: OBJECTIVE
  The study of the grounds on which data regulatory authorities base their decisions on drug safety evaluations is an important clinical and public health issue. The aim of this study was to review the type and publication status of data sources supporting benefit/risk ratio re-evaluations conducted by the major regulatory authorities on safety issues.
  
  
  METHODS
  A website search was carried out to identify all safety alerts published by the U.S Food and Drugs Administration, Health Canada, European Medicines Agency and the Australian Therapeutics Goods Administration. Safety alerts were included if the causal relation between a suspected drug exposure and the occurrence of an adverse event was evaluated for the first time between 2010 and 2012. Type of data sources evaluated by these regulatory authorities, publication status of the data sources and status of the drug label section with respect to updating were evaluated.
  
  
  RESULTS
  A total of 59 safety alerts were included in this study. Of these, 33 (56%) were supported by post-marketing spontaneous reports, 24 (41%) evaluated randomized clinical trials, 16 evaluated cohort studies (27%), 13 were case-control studies (22%) and 11 evaluated case report/case series (17%). Twenty-three safety alerts (39%) were issued based. on unpublished evidence, corresponding mainly to post-marketing spontaneous reports. The "Warnings and precautions section" was the drug label section most frequently updated (n = 40; 68%).
  
  
  CONCLUSIONS
  Despite the different lengths of time taken by the different regulatory authorities to come to similar decisions on the same issues-an issue which would seem to deserve further harmonization-post-marketing spontaneous reports have supported most of the benefit/risk ratio re-evaluations, thereby confirming the value of such re-evaluations in detecting unknown adverse events.
authors.affiliation: Centre for Health Technology Assessment and Drug Research (CHAD), Association for Innovation and Biomedical Research on Light and Image (AIBILI), Azinhaga de Santa Comba, Celas, Coimbra, 3000-548, Portugal, carlosmiguel.costaalves@gmail.com.
authors.forename: Carlos
authors.initials: C
authors.lastname: Alves
authors.forename: Ana Filipa
authors.initials: AF
authors.lastname: Macedo
authors.forename: Francisco Batel
authors.initials: FB
authors.lastname: Marques
mesh_terms: D003257:Consumer Product Safety; D003625:Data Collection; D004335:Drug and Narcotic Control; D064420:Drug-Related Side Effects and Adverse Reactions; D035082:Federal Government; D033161:Government Regulation; D011358:Product Surveillance, Postmarketing
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