Role of external evidence in monitoring clinical trials: experience from a perinatal trial

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Abstract
The randomised controlled trial is the most scientifically rigorous way of evaluating interventions whose effects on important clinical outcomes are uncertain.1 Before conducting such a trial, investigators should undertake a systematic review of thevidence from existing trials, including, if appropriate, a meta-analysis. This prevents trials being carried out unnecessarily when the answer to the clinical question is already known.A priori power calculations should be made to determine how many participants will be required to answer the research question,2 and this process is increasingly being required by research ethics committees and funding bodies, among others.3 Nevertheless, under some circumstances recruitment to a trial may be halted before the planned sample size has been reached because The process for stopping a trial early because of indications from internal data is well accepted and recognised and the statistical methodology has been discussed at length, but this is not the case for external evidence. The process by which trial investigators should consider external evidence and make decisions concerning further recruitment is unclear. #### Summary points Principal investigators of clinical trials should be responsible for obtaining relevant information emerging from other studies Investigators should seek unpublished confidential information, but this requires sensitive handling Meta-analysis is useful for incorporating ongoing trial data with existing and emerging evidence The trial data monitoring committee is responsible for reviewing both internal and external information, but the trial steering committee should decide whether to modify or stop a trial We describe our recent experience of stopping a large international trial because of external evidence …