title: Modulating the design of clinical trials to address the question of mechanisms of disease.
abstract: The evaluation of causation of a disease is judgemental. It should be based on an overview of how far the observed association satisfies several criteria, including its strength, dose response, temporal sequence, independence, consistency, presence of a plausible mechanism, predictive power, and reversibility. Whilst the results of randomised controlled trials are frequently incorrectly considered as proof (or otherwise) of causation, what they do allow is an evaluation of the reversibility of disease. Whilst reversibility is one of the criteria which allows causation to be judged and randomised trials are reasonably considered as the 'gold standard' study design, they do not necessarily shed light on mechanisms of disease, particularly in the context of chronic degenerative disorders such as those underpinned by the atherosclerotic process.
authors.affiliation: NHLI, Faculty of Medicine, Imperial College London, London, UK. n.poulter@imperial.ac.uk
authors.forename: Neil R
authors.initials: NR
authors.lastname: Poulter
mesh_terms: D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000209:etiology*; D016032:Randomized Controlled Trials as Topic / Q000379:methods*