Planning for closeout — From Day One

Abstract

Clinical trials are often stopped prematurely by Data and Safety Monitoring Boards, sponsors, or the investigators for reasons such as unexpected harmful effects of the intervention, clear lack of benefit, or futility due to sluggish recruitment or an unexpectedly low outcome rate in the placebo group. Planning for closeout, however, usually does not begin until after the trial is well underway. This article describes the experience of the Heart and Estrogen/progestin Replacement Study (HERS) investigators when data from the first year of follow-up revealed a clear but non-significant divergence in outcome rates between the treatment groups, and planning for early closure was initiated. Three advantages of beginning early to plan for closeout are described and approaches to planning closeout are suggested.