Journal of the Royal College of Physicians of London
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J R Coll Physicians Lond · Mar 1995
ReviewMega-trials: methodological issues and clinical implications.
A recent development of the therapeutic trial has been the mega-trial: a large, simple randomised trial analysed on an 'intention to treat' basis. Mega-trials have advantages in terms of increased statistical power, but also raise several new questions of interpretation. In mega-trials, randomisation serves to achieve identical allocation groups in a situation where there is poor experimental control and a large measure of between-subject variation. ⋯ In this sense, mega-trials can be repeated but cannot be replicated. Basic science and clinical science both seek understanding at the level of the individual subject; but in a mega-trial, analysis is only meaningful at the group level. The non-scientific nature of mega-trials derives from their methodology, which dispenses with the scientific aim of maximum experimental control to remove or minimise bias, and instead uses randomisation to achieve an equal distribution of bias between groups.