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

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

• Funding has run out or further recruitment has become impossible because of a lack of interest in the participating centres—“trial fatigue”

• The internal evidence emerging from accumulating trial data suggests that continuing would be unethical4

• External evidence indicates that the trial should be halted.5

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.