Mega-trials: is meta-analysis an alternative?
Large scale placebo-controlled trials with clinical end-points are not possible when other compounds with proven efficacy are already available. Hence, the question arises whether the available experience from placebo-controlled phase III trials can be analysed jointly to assess whether an effect on clinical end-points exists. This question was answered for the new ACE inhibitor ramipril, with which five exercise capacity trials were done in similar patients with heart failure. Meta-analysis showed that ramipril reduced the occurrence of the combined event death or hospitalisation by 32% (P = 0.05), based on the customary 'intention-to-treat' comparison for large scale trials. From this analysis, the lesson has been learnt that a drug development programme must be carefully planned to allow for this type of meta-analysis.
Lubsen
J
J
SOCAR Research SA, Givrins, Switzerland.
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D015201:Meta-Analysis as Topic; D017257:Ramipril / Q000627:therapeutic use*
D000806:Angiotensin-Converting Enzyme Inhibitors; D017257:Ramipril