title: [Non-inferiority trial used in venous thromboembolic disease. A warily interpretation is necessary!].
abstract: BACKGROUND
  Equivalence trials are actually frequently used to prove non-inferiority in anticoagulant therapy. Equivalence trials consist to demonstrate that two treatments are not too much different. This difference has to be under a margin previously determined. The margin corresponds to an efficacy loss that is defined to be acceptable, in accordance to the advantages due to the new treatment. The aim of this work is to explore the equivalence trial published in the thromboembolic disease by focus on the non-inferiority margin used.
  
  
  METHODS
  We identified published equivalence trials in the venous thromboembolic disease, by a systematic search in Medline. We calculated the efficacy loss by reference with the value of the smallest effect size of the standard treatment compared to placebo.
  
  
  RESULTS
  We found 9 equivalence trials used in venous thromboembolic disease. The mean value of the efficacy loss was 434%, and the median value was 357%. Eighty-five percent of the values of the efficacy loss were above 100%.
  
  
  CONCLUSIONS
  Eighty-five percent of the equivalence trials conclude to equivalence despite a complete efficacy loss of the effect of the standard treatment compared to placebo. The results of equivalence trials should be interpreted warily. The corresponding non-inferiority margin should be chosen more rigorously and by reference with the value of the smallest effect size of the standard treatment compared to placebo.
authors.affiliation: Service de médecine interne, hôpital Edouard-Herriot, place d'Arsonval, 69008 Lyon, France. laurent.perard@chu-lyon.fr
authors.forename: L
authors.initials: L
authors.lastname: Pérard
authors.forename: A
authors.initials: A
authors.lastname: Hot
authors.forename: M
authors.initials: M
authors.lastname: Cucherat
authors.forename: M
authors.initials: M
authors.lastname: Simon
authors.forename: H
authors.initials: H
authors.lastname: Desmurs
authors.forename: B
authors.initials: B
authors.lastname: Coppéré
authors.forename: M-H
authors.initials: MH
authors.lastname: Girard-Madoux
authors.forename: J-P
authors.initials: JP
authors.lastname: Boissel
authors.forename: J
authors.initials: J
authors.lastname: Ninet
mesh_terms: D000925:Anticoagulants / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D006493:Heparin / Q000627:therapeutic use; D013810:Therapeutic Equivalency; D013923:Thromboembolism / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D006493:Heparin