The general concepts of an equivalence trial, applied to ASSENT-2, a large-scale mortality study comparing two fibrinolytic agents in acute myocardial infarction

About a decade ago clinical trials were almost exclusively ‘superiority’ trials. This situation has changed, and nowadays ‘equivalence’ trials have gained popularity. Loosely speaking, the intention of an equivalence trial is to show that two treatments have about the same therapeutic effect. This is in contrast to a superiority trial, where the purpose is to show superiority of the new active treatment over placebo or over the standard active treatment. Thus, the goals set for an equivalence trial are less ambitious than the goals set for a superiority trial. Why then the recent interest in equivalence trials? For new drugs within a particular pharmacological class it is becoming increasingly difficult to improve upon existing treatments. In particular, the introduction of thrombolytics for acute myocardial infarction patients has significantly decreased the 30-day mortality over the last two decades from about 10% to 6·3% in GUSTO-1. A further reduction in mortality is therefore not very likely. While one might strive for new thrombolytic treatment to be superior to existing treatment, it is more realistic to hope for an equally good performance regarding mortality and to focus on other possible benefits of the new treatment, such as: side effects, cost, ease of administration. There may be several reasons why the equivalence of two treatments is of scientific and economic interest.