Individual participant data meta-analyses of adverse event data from randomized controlled trials of statin therapy
The Cholesterol Treatment Trialists’ (CTT) Collaboration was established in 1994, with its initial protocol being published in 1995. It was set up after it was recognized that no single lipid intervention trial would be likely to have sufficient statistical power to reliably assess mortality outcomes or look at events in particular types of patient. Its aim is to conduct periodic meta-analyses of large-scale (≥1000 participants), long-term (≥2 years scheduled treatment duration) unconfounded, randomized controlled trials of lipid intervention therapies.
The CTT Collaboration's previous work has largely focused on statin therapy, with individual participant data (IPD) on major vascular events, cancers and mortality having been collected from about 30 major statin trials (equating to approximately 175,000 trial participants). The analyses of such data have been published in the Lancet, showing that reduction of LDL cholesterol using statins substantially reduces the risk of major vascular events vascular mortality by about one fifth for each 1 mmol/L reduction in LDL cholesterol achieved in a wide range of people, but that statin therapy does not increase the risk of non-vascular causes of death or of cancer.
It is now known that statins produce small excess risks of myopathy (and more rarely, of rhabdomyolysis), and that they increase the risk of new-onset diabetes mellitus, and also probably of haemorrhagic stroke, but these risks are small. However, there has recently been an upsurge in public concern that statins may cause a wider range of side-effects such as muscle pain, depression, cognitive impairment and cataracts. These concerns have received considerable media coverage, and many people at risk of cardiovascular disease have endangered their health by stopping statin medication.
To address these concerns, the CTT Collaboration is extending the CTT IPD meta-analysis dataset to encompass all recorded adverse events for each of the participating trials so as to provide a more complete understanding of the nature and magnitude of any other effects (either adverse or beneficial) of statin therapy.
Research Experience, Research Methods and Training
- Working with senior staff to carry out analyses specified in the CTT 2016 protocol (http://www.ahjonline.com/article/S0002-8703%2816%2900032-6/pdf).
- 2. Interpreting the findings of these meta-analyses.
Field Work, Secondments, Industry Placements and Training
Students will learn to collaborate with trialists, follow statistical analysis plans, use medical coding dictionaries, interpret analyses and draft manuscripts.
A clinically qualified doctor, or graduate in a related subject, with highly developed numeracy skills and an interest in the field of cardiovascular medicine.