Clinical management of acute myocardial infarction has been strongly influenced by large, simple trials (mega-trials) with unrestrictive protocols and limited data collection.
The design has been adopted to increase statistical power to a maximum.
Its validity rests on an effective randomisation procedure and intention-to-treat analysis of deaths.
Experience has shown that mega-trials tend to generate effect-estimates nearer the null than those from conventional trials or meta-analyses.
When a small or absent observed treatment effect (or subgroup effect) in a mega-trial contrasts with the results of conventionally designed trials, it is necessary to assess both null bias and failure to increase the true treatment effect to a maximum in the mega-trial.
Null bias will arise when the contrast between treatment and no-treatment, or between subgroups, is blunted either by non-protocol therapy or by inaccuracy of data, including misclassification between subgroups.
Each is more likely with an unrestrictive design.
To increase the true treatment effect to a maximum, trial conditions must be specified with insight into mechanism, dose-dependence, and time-dependence.
The mega-trial design is therefore unsuited to an exploratory role.
These issues are illustrated by the examples of nitrates, angiotensin-converting-enzyme inhibitors, and magnesium in acute myocardial infarction but have general relevance to the validity and generalisability of simple trials.
Mots-clés Pascal : Appareil circulatoire pathologie, Cardiopathie coronaire, Traitement, Homme, Infarctus, Myocarde, Essai thérapeutique contrôlé, Méthodologie, Royaume Uni, Europe, Myocarde pathologie
Mots-clés Pascal anglais : Cardiovascular disease, Coronary heart disease, Treatment, Human, Infarct, Myocardium, Controlled therapeutic trial, Methodology, United Kingdom, Europe, Myocardial disease
Notice produite par :
Inist-CNRS - Institut de l'Information Scientifique et Technique
Cote : 95-0516430
Code Inist : 002B12A03. Création : 01/03/1996.