Randomised trials lie at the heart of the practice of evidence-based clinical medicine. Over the last 40 years, results from large randomised trials have led to widespread use of effective cardio-protective drugs and the avoidance of millions of premature deaths and non-fatal major vascular events.

Examples from lipid-lowering and diabetes trials which have had an important impact will be used to illustrate evolving methods for delivering streamlined and cost-effective trials that answer important clinical questions. Wider dissemination of such methods is essential to ensure that late phase trials remain viable in the light of the rising costs and complexity of trials run by the pharmaceutical industry.