The MRC/BHF Heart Protection Study was a landmark randomised trial completed in the 1990s that showed the benefits of lowering-cholesterol in over 20,000 individuals at high-risk of vascular disease. The results above show the benefit of cholesterol-lowering with simvastatin for a wide-range of vascular outcomes.
We know that routine breast cancer screening is beneficial in women aged 50-70, but the effects in slightly younger and older women is still uncertain. In response to this, the AgeX trial was established in 2010 offering additional screening to women aged 47-49 and 71-73. Randomisation is by means of clusters to include women invited for screening with their counterparts who are not invited for screening at 65 of the 80 breast cancer screening centres in England.
Niacin lowers LDL cholesterol and raises HDL cholesterol. The THRIVE trial randomly assigned more than 25,000 patients with vascular disease to receive either extended-release niacin with laropiprant or matching placebo. 245 sites were located in the UK, Scandinavia and China. During a median follow-up of 3.9 years, participants randomly assigned to niacin had lower LDL cholesterol and higher HDL cholesterol compared to matching placebo in patients whose LDL cholesterol had been standardized through prior statin therapy.
Vist et al (2008) have attempted to answer this question by comparing people who participate in a randomised with their counterparts who did not take part in a particular trial. Whilst longitudinal follow-up of participants was possible for trial volunteers, such data was not readily available for people who did not participate.
The starting point to do a trial well is to identify an important question to address. So much better, if this question emerges from a meta-analysis of the existing evidence as was the case with the ATLAS trial. The Early Breast Cancer Trialists Collaborative Group identified a number of small trials comparing 10 years treatment with tamoxifen with 5 years, but these early trials were too small to reliably assess the effects of longer treatment.