Thrombolysis or nothing for acute myocardial infarction? It's all the same!
BACKGROUND
The methodological and ethical value of equivalence and non-inferiority trials is questioned. These studies are still increasingly used in drug evaluation and accepted by the scientific community and the regulatory authorities.


CONCLUSIONS
By applying the hypothesis of an equivalence trial of saruplase and streptokinase (SK) we proved that the no-thrombolysis approach in the GISSI trial was equivalent to thrombolysis with SK, i.e. death rates in patients given SK or not were similar enough to consider the no-thrombolysis regimen equivalent to thrombolytic treatment. These data illustrate the unreliability of equivalence trials, which can even disprove consolidated clinical evidence such as the efficacy of thrombolysis in acute myocardial infarction. Equivalence trials should not be considered an option by the scientific community and should not be accepted as a basis for marketing authorization by the regulatory authorities. AIMS To assess the reliability of equivalence trials we tested whether the no-thrombolysis approach was equivalent to thrombolysis with streptokinase (SK) in acute myocardial infarction.


METHODS
We applied the hypothesis of an equivalence trial of a recombinant plasminogen activator and SK to the GISSI-1 control group.


RESULTS
In at least one of three subsets randomly extracted from the GISSI database the equivalence criterion was satisfied, i.e. death rates in patients given SK or not were similar enough to consider the no-thrombolysis regimen equivalent to thrombolytic treatment. Two-thirds of 100 replications of the sampling gave this result.


CONCLUSIONS
These findings suggest the unreliability of equivalence trials, which should neither be adopted by the scientific community nor accepted by the regulatory authorities.
Bertele'
Vittorio
V
Mario Negri Institute for Pharmacological Research, Milan, Italy. bertele@marionegri.it
Angelici
Laura
L
Barlera
Simona
S
Garattini
Silvio
S
D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D009203:Myocardial Infarction / Q000188:drug therapy*; D010960:Plasminogen Activators / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D013223:Statistics as Topic; D013300:Streptokinase / Q000627:therapeutic use*; D013810:Therapeutic Equivalency; D015912:Thrombolytic Therapy / Q000379:methods* / Q000592:standards; D014568:Urokinase-Type Plasminogen Activator / Q000627:therapeutic use*
D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D013300:Streptokinase; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator; C067551:saruplase