Fundamental deficiencies in the megatrial methodology


Charlton, Bruce G. 2001. Fundamental deficiencies in the megatrial methodology. Current controlled trials in cardiovascular medicine. 2 (1), pp. 2-7.
AuthorsCharlton, Bruce G.

The fundamental methodological deficiency of megatrials is deliberate reduction of experimental control in order to maximize recruitment and compliance of subjects. Hence, typical megatrials recruit pathologically and prognostically heterogeneous subjects, and protocols typically fail to exclude significant confounders. Therefore, most megatrials do not test a scientific hypothesis, nor are they informative about individual patients. The proper function of a megatrial is precise measurement of effect size for a therapeutic intervention. Valid megatrials can be designed only when simplification can be achieved without significantly affecting experimental control. Megatrials should be conducted only at the end of a long process of therapeutic development, and must always be designed and interpreted in the context of relevant scientific and clinical information.

Keywordsepidemiology; history; megatrial; methodology; randomized trial; therapeutic intervention
JournalCurrent controlled trials in cardiovascular medicine
Journal citation2 (1), pp. 2-7
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PrintJan 2001
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Deposited11 Aug 2009
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Charlton, B. G. (2001) ‘Fundamental deficiencies in the megatrial methodology.’ Current controlled trials in cardiovascular medicine 2(1) 2-7.

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