Clinical Trials

❘❙❚■ Chapter 38 | Meta-AnalysisWhat is a meta-analysis?Gene Glass first used the term ‘meta-analysis’ in 1976 to refer to a philosophy,not a statistical technique. Glass suggested that reviewing the literature in itselfwas a research technique and should therefore be performed as systematically asmore formal research. Since then, the term meta-analysis has meant literally ananalysis of several individual analyses or studies, or an amalgamation of previouslypublished and unpublished research on a specific intervention. To perform ameta-analysis, the results of two or more independent studies are combined ina meaningful way that still addresses the original clinical question. The outputfrom a meta-analysis typically consists of an overall mean treatment difference,derived from a weighted average of the treatment difference from each study anda confidence interval. The weighting given to each study depends on its quality,precision, and size.For example, we recently conducted a meta-analysis on the impact of beta-blockerson mortality in patients with heart failure. Twenty-two relevant studies wereidentified. While the largest single trial had 3,991 patients and the smallest had just12 patients, the meta-analysis had a total of 10,480 patients [1]. Table 1 displays thedifferences in the mortality rates of 14 of the individual studies that had at least onedeath in each treatment arm. The meta-analysis shows that beta-blockers reducethe odds of death by about one-third [1], an effect somewhat different from theresults of many of the 14 studies.What is the aim of a meta-analysis?The aim of a meta-analysis is to estimate the treatment effect with the greatestpossible power and precision [2–5]. By including the study populations of severaltrials, a real treatment difference can be detected more easily due to an increasedsample size, and the precision of estimating that difference is improved. A wellconductedmeta-analysis is time consuming and expensive, but it is still unlikely tobe as expensive as conducting a new, larger trial.What basic steps are involved in a meta-analysis?There are five steps involved in a meta-analysis [4,6]:Step 1: Formulation of the study questionThe aim of the analysis should be specific and clear, for example:“Do beta-blockers reduce mortality in patients with heart failure when used inaddition to standard therapies?”440