SeriesOvercoming the limitations of current meta-analysis of randomised controlled trials
Section snippets
Protocol development
A well-designed RCT begins with identification of a medically important question. A protocol is developed before the trial begins, so that conduct of the trial follows a prospective plan. The design revolves around the primary and sometimes secondary hypotheses, which are usually parsimonious. These hypotheses drive the inclusion and exclusion criteria, the choice of specific treatment regimen, study outcomes, subgroups of interest, and analysis plan. All are generally defined in advance and
Key issues in conduct of a well-designed meta-analysis (panel 1)
For a meta-analysis to provide reliable information, it should meet, at least, the same qualitative and quantitative standards as a single well-designed large RCT. Several of the standards applied in the conduct of a well-designed RCT can be adopted, so that a more prospective approach to meta-analysis is taken.
Updating of meta-analysis
There have been recommendations for continuous updating of meta-analysis as each new RCT is published.8, 27 The principles of the OIS and application of formal monitoring guidelines provide a framework for examination of this issue. First, updating of meta-analysis should be periodic (not continuous, since this clouds the interpretation of any differences observed) when a significant increment in additional information is available—for example, when the increment in new information is at least
Disorders with few large trials
Many of the judgments and principles that govern the need for a large amount of information (from either RCTs or a meta-analysis of trials) are applicable to many specialties, not just cardiology, for which several examples are given. The development of both large trials that are affordable and meta-analysis, even in cardiology, is recent. Although a few moderate-sized (a few thousand patients and a few hundred events) RCTs in cardiology were completed in the 1970s, it has only been since the
Summary of standards and interpretation of meta-analysis
This paper provides guidelines for the conduct, analysis, and interpretation of meta-analysis, summarised in Panel 1, Panel 2. In general, we believe that meta-analysis should be at least as rigorous as a well-designed and adequately powered RCT. Despite reasonable assumptions, there may be good reasons to use more conservative statistical criteria for a meta-analysis than one would for an RCT. There are widely recognised potential biases inherent even in the best meta-analysis. Therefore, more
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