Meta-Analysis, Review and Update of Methodologies

In 1982 thrombolytic therapy for acute coronary syndromes was controversial. In a meta-analysis of 7 trials Stampfer et al. found a reduced risk of mortality of 0.80 (95% confidence interval 0.68–0.95). These findings1 were not accepted by cardiologists until 1986, when a large clinical trial confirmed the conclusions2 , and streptokinase became widely applied.

Meta-analyses can be defined as systematic reviews with pooled data. Traditionally, they are post-hoc analyses. However, probability statements may be more valid, than they usually are with post-hoc studies, particularly if performed on outcomes that were primary outcomes in the original trials. Problems with pooling are frequent: correlations are often nonlinear3; effects are often multifactorial rather than unifactorial4; continuous data frequently have to be transformed into binary data for the purpose of comparability5; poor studies may be included and coverage may be limited6 ; data may not be homogeneous and may fail to relate to hypotheses.7 In spite of these problems, the methods of meta-analysis are an invaluable scientific activity: they establish whether scientific findings are consistent8 , and can be generalized across populations and treatment variations9 , and whether findings vary between subgroups.10 The methods also limit bias, improve reliability and accuracy of conclusions11, and increase the power and precision of treatment effects and risk exposures.6

Keywords

Cholesterol Angiotensin Smoke Stein Pravastatin 

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