Mega trials

Mega-trials Statistical complexity Few inclusion/exclusion criteria Representativeness to treated population known only toward the end of the trial... 

When it is suspected that there may only be small differences between active treatments, and when placebo controls are unavailable for clinical or ethical reasons, then it is often necessary to resort to large-scale studies ( mega-trials ). A good, famous example was the clinical trial known by the acronym GUSTO, where streptokinase and recombinant tissue plasminogen activator (t-PA) were compared for acute coronary thrombosis (for a commentary, see Hampton, 1996). 

Hampton JR. 1996. Alternatives to mega-trials in cardiovascular disease . Cardiovasc. Drugs Ther. 10 759-765. 

Very large (mega) trials, including thousands of patients, are the best way of asking... 

I Psychiatrists have been overreliant on the pharmaceutical industry to evaluate new products and have failed to date to conduct any independent large/mega trials. 

Fibrinolysis Unsuccessful mega-trials GISSI, trials of PCI TIMI flow grades ISIS-2, and ASSET after lysis FDA approval TAM I, ECSG,... 

Cleland JG, Freemantle N, Coletta AR Clark AL. Clinical trials update from the American Heart Association REPAIR-AMI, ASTAMI, JELIS, MEGA, REVIVE-II, SURVIVE, and PROACTIVE. Eur J Heart Fail 2006 8 105-1 10. 

Freeman CD, Strayer AH. Mega-analysis of meta-analysis an examination of meta-analysis with an emphasis on once-daily aminoglycoside comparative trials. Pharmacotherapy 1996 16(6) 1093-102. 

O Donoghue ML, Braunwald E, Antman EM, Murphy SA, Bates ER, Rozenman Y, Michelson AD, Hautvast RW, Ver Lee PN, Close SL, Shen L, Mega JL, Sabatine MS, Wiviott SD. Pharmacodynamic effect and clinical efficacy of clopidogrel and prasugrel with or without a proton-pump inhibitor an analysis of two randomised trials. Lancet 2009 374(9694) 989-97. 

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