CONTINUOUSLY MONITORED STOPPING BOUNDARY METHODOLOGIES - THE ISSUES OF SENSITIVITY, ASSOCIATION AND TRIAL SUSPENSION

Thall et al, consider a continuous monitoring strategy for multiple di screte outcomes to determine whether a trial should terminate early. W e evaluate important issues raised in the application of a continuous monitoring strategy for multiple outcomes. Specifically, we evaluate: (i) the sensitivity of such a methodology to small perturbations in th e stopping boundaries; (ii) the need to employ accrual buffers when a trial approaches a stopping boundary - a large buffer implying that te mporary suspension is unwarranted; and (iii) the role of association a mong the multiple outcomes of interest. Simulation studies demonstrate that the methodology is sensitive to small perturbations in the stopp ing boundaries, that the size of an accrual buffer can vary widely ove r the course of a trial, and that the extent of association among mult iple outcomes plays a large role in determining the stopping propertie s of a trial. We illustrate these issues using the HLA non-identical d onor bone marrow transplant trial, with two discrete outcomes. (C) 199 7 by John Wiley & Sons, Ltd.