Some practical issues in the design, monitoring and analysis of a sequential randomized trial in pressure sore prevention

A sequential double blind (assessor and patient) triangular design was used to compare the incidence of pressure sores following elective major surger y among patients lying on a standard foam mattress with those on a dry visc o-elastic polymer pad during their operation. A total of 446 patients were recruited into the trial between 1994 and 1996. Interim analyses were carri ed out after 181 patients were entered into the trial and then subsequently after approximately every 100 patients recruited. The trial unexpectedly r eached a stopping boundary at the first interim analysis, however the Indep endent Data Monitoring Committee recommended continuation of the trial. The y were concerned that there was a need for a larger definitive trial and ab out an apparent treatment by centre interaction. They required a substudy t o be undertaken to further validate the subjective endpoint, and that furth er sensitivity analyses of the main trail endpoint should be carried out in the second interim analysis. The trial was stopped at the third interim an alysis when again a stopping boundary was crossed indicating that the gel p ad was associated with significantly fewer pressure sores than the standard mattress (log odds ratio -0.7, (95 per cent confidence interval (CI), -1.2 8,-0.11), p=0.02) (estimate CI, p-value adjusted for group sequential condu ct). The design, monitoring and analysis of this trial will be presented as an example of the practical problems or non-problems encountered for the l ocal hospitals, for the trials unit, for the data monitoring committee and for the funding committee. Copyright (C) 2000 John Wiley & Sons, Ltd.