title: Differences between clinical trials and postmarketing use.
abstract: OBJECTIVE
  Clinical trials constitute the gold standard to assess the efficacy and safety of new medicines. However, because they are conducted in standardized conditions far from the real world of prescription and use, discrepancies in patient selection or treatment conditions may alter both the effectiveness and risks. On the basis of three examples, our objectives were to study the differences between the characteristics of treated populations and treatment patterns in clinical trials and in postmarketing settings and to discuss the potential consequences on actual efficacy and safety.
  
  
  METHODS
  Treated populations were compared with patients included in premarketing clinical trials. Comparisons were made on the basis of demographic characteristics and treatment patterns.
  
  
  RESULTS
  Whatever the indicator and the drug studied, differences were observed: from 0.04% to 63% for tacrine, from 0% to 37% for celecoxib and from 6% to 52% for simvastatin, with possible consequences on the effectiveness and safety of the drug concerned. Our results confirm the under-representation of women and elderly patients in premarketing clinical trials, e.g. an M : F ratio of 4.6 in clinical trails of simvastatin vs 1.0 in the joint population. Moreover, the concomitant use of medicines was made extremely restrictive by the protocols of these trials while this was not the case in the postmarketing phase. This has possible consequences on the effectiveness and safety of the drug concerned.
  
  
  CONCLUSIONS
  These results plead for systematic ad hoc observational postmarketing studies for any novel and/or expensive medicine to assess the relevance of premarketing data.
authors.affiliation: Département de Pharmacologie, Université Victor Segalen, Bordeaux 2, Bordeaux, France. karin.martin@pharmaco.u-bordeaux2.fr
authors.forename: Karin
authors.initials: K
authors.lastname: Martin
authors.forename: Bernard
authors.initials: B
authors.lastname: Bégaud
authors.forename: Philippe
authors.initials: P
authors.lastname: Latry
authors.forename: Ghada
authors.initials: G
authors.lastname: Miremont-Salamé
authors.forename: Annie
authors.initials: A
authors.lastname: Fourrier
authors.forename: Nicholas
authors.initials: N
authors.lastname: Moore
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000068579:Celecoxib; D002986:Clinical Trials as Topic; D000075202:Contraindications; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011358:Product Surveillance, Postmarketing; D011720:Pyrazoles; D019821:Simvastatin / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*; D013619:Tacrine / Q000627:therapeutic use*
chemical_list: D011720:Pyrazoles; D013449:Sulfonamides; D013619:Tacrine; D019821:Simvastatin; D000068579:Celecoxib