Large-scale Randomised Evidence

Reliable assessment of the treatment and prevention of cardiovascular disease

When important causes of vascular disease are assessed, their effects are sometimes so extreme that cause-effect relationships can be reliably inferred from observational studies of sufficiently large size. But, the effects of treatments may well involve only moderate improvements in mortality and major morbidity. Just a moderate survival improvement in vascular disease might, however, save tens of thousands of lives a year (and prevent much disability). So, even when the absolute gain is only moderate it is important not to get wrong answers. The best way to obtain reliable results about moderate treatment effects is by producing large-scale randomised evidence: large numbers avoid being misled by the play of chance and proper randomisation avoids being misled by biases.

As one way of achieving this aim, Oxford research groups pioneered the use of collaborative "meta-analyses" of previous randomised trials that had addressed much the same therapeutic question. These meta-analyses in vascular disease (in particular, those involving trials of antithrombotic, fibrinolytic and lipid-lowering therapy) have substantially influenced both worldwide clinical practice and future research strategies. Oxford also established the use of very large streamlined randomised trials, or "mega-trials", to assess the effects of widely practicable treatments on mortality and major morbidity. Such trials typically randomise some tens of thousands of patients and, as a result, have provided clear and reliable information about the effects of many treatments (such as aspirin and fibrinolytic therapy for the emergency treatment of heart attacks, and statin therapy for a very wide range of patients with vascular disease, diabetes or hypertension irrespective of age, sex or presenting cholesterol level). The consequent widespread use of these effective treatments is preventing hundreds of thousands of premature deaths each year around the world.

PIs involved in this research theme:

Prof Rory Collins - (Theme Leader)

Prof Jane Armitage

Prof Colin Baigent

Prof Zhengming Chen

Dr Martin Landray

Dr Sarah Parish