Incorporation of sequential trials into a fixed effects meta-analysis

The technique of meta-analysis provides a systematic and quantitative approach to the summary of results from a collection of similar randomized studies. Comprehensive methodology exists for analysis when all trials are of a fixed sample size design, but this is based on assumptions which are no longer valid when incorporating sequentially designed studies. In this paper the effect of incorporating one or more sequential trials into a meta-analysis otherwise consisting of fixed sample size trials is investigated. The results from simulation studies of a variety of plausible scenarios are presented. The aim is to quantify the extent to which bias is introduced. It was found that when incorporating two alternative sequential designs, the triangular test and the O'Brien and Fleming procedure, the results of a conventional meta-analysis remain accurate.