Sequential Meta-analysis of Past Clinical Trials to Determine the Use of a New Trial

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Abstract
Background: Clinical trials can be stopped early based on interim analyses or sequential analyses. In principle, sequential analyses can also be used to decide whether enough evidence has been gathered in completed trials to make further trials unnecessary. We demonstrate such an application through a retrospective analysis of clinical trials comparing ventilation methods for the treatment of preterm newborns. Methods: We identified 5 recent trials that compared high-frequency ventilation with conventional mechanical ventilation in the treatment of preterm newborns. Death or chronic lung disease and chronic lung disease in survivors were the primary clinical outcomes of interest. We applied sequential meta-analyses to these 5 studies. Results: After including the first study of the last 5 trials in a sequential meta-analysis, the boundary of "no clinically relevant effect" was crossed for both outcomes (death or chronic lung disease). A sensitivity analysis using a reduction in the size of assumed clinically relevant effect showed the same findings after 2 trials. Conclusions: Sequential meta-analyses showed that a lack of clinically relevant effect had been established after the first of the 5 trials. If such an analysis had been conducted after the first or second of these clinical trials, it might have led to changes in the study design of subsequent trials or even to a reassessment of the need for further trials.