Answers to complex questions cannot be derived from “simple” trials

As we progress in the exciting area of treatment of acute myocardial infarction, two clinical trial methodologies coming from different philosophies and traditions must be considered. Smaller (200-3000 patient), detailed trials focusing on pathophysiology will be referred to as "mini-trials", while mammoth studies (10 000-50 000 patients) designed to measure mortality rates will be referred to as "mega-trials." In the field of coronary thrombolysis, examples of minitrials include the continuing efforts of the Thrombolysis in Myocardial Infarction (TIMI) Group, the European Cooperative Study Group (ECSG), and the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) Group.`8 The major mega-trials have been conducted by the Gruppo Italiano Per Lo Studio Della Streptochinasi Nell' Infarcto Miocardico (GISSI) and the International Studies of Infarct Survival (ISIS) Groups."'1 Both types of trials have proved to be essential to our understanding of thrombolytic intervention, and in most ways the two designs are quite complementary. In this paper, in contrasting the two designs, we will highlight the critical contribution of the minitrials and then provide insight into the opportunity provided in an ongoing mega-trial to investigate the differences in the approaches (table).