Meta-analysis of randomized trials: looking back and looking ahead.

Meta-analyses as currently practiced are usually retrospective. They can be made more rigorous by developing a protocol that incorporates prospectively the elements that are usually necessary in a well-designed trial. Meta-analysis and large trials are complementary. Meta-analysis of small trials is useful in generating the hypotheses and assisting in the design of the large trials that are needed. Once the large trials have been completed, they could be brought together within the framework of a meta-analysis to estimate the overall treatment effect with greater confidence and to explore the effects in various subgroups. This article explores the value and limitations of meta-analyses and suggests ways of improving their conduct and interpretation.