This programme aims to generate reliable evidence about widely applicable and cost-effective treatments using cost-effective randomised trials in a range of diseases which contribute substantially to the global burden of disease. Over the last several years, CTSU has developed streamlined methods to recruit large numbers of patients and conduct trials cost-effectively (e.g. ASCEND), including using factorial designs to address more than one question at a time (e.g. HPS, SEARCH, ASCEND), and to use record linkage to facilitate follow-up, both during the trial (e.g. ASCEND, 3C) and in the longer term (e.g. HPS, SEARCH). In addition, CTSU has been planning and piloting new trials of non-commercial questions (e.g. high-dose vitamin-D in older people) and collaborating with many other researchers in the design, conduct and analysis of trials in a range of other conditions, such as neurodegenerative disease, leukaemia, carotid artery disease etc. Our previous trials using these large streamlined designs have been able to reliably answer important public health questions. For example, the SEARCH trial clearly showed that lowering homocysteine using folic acid with vitamin-B12 while safe had no benefit in terms of major vascular events or other important outcomes, such as coronary events, stroke or cancer incidence. A further example of a large streamlined highly cost-effective trial is the ongoing ASCEND trial which has randomised over 15,000 diabetic patients without clinically manifest arterial disease to aspirin and/or omega-3 fatty acids (with matching placebos using a 2x2 factorial design) to assess their effects on cardiovascular disease, cancer and other major outcomes. CTSU has also played a key role over a number of decades in the MRC leukaemia trials in adults and children which have made a major contribution to the significant improvements in survival of these patients such that now most patients with leukaemia or lymphoma in childhood can expect to be cured and to live normal lives for decades afterwards. Our future programme of work will involve the long-term follow-up of some of our existing trials, for example, HPS to assess the long term benefit or risks of vitamin supplementation (vitamin-E, -C and β-carotene), the completion of the main phase of follow-up in ASCEND (with the main results expected in 2017) and to commence a number of new major trials, including a study of high-dose vitamin-D to prevent fractures, cancer and cardiovascular disease in older people and various trials to evaluate treatments in chronic kidney disease.