THE EARLY TERMINATION OF CLINICAL-TRIALS - CAUSES, CONSEQUENCES, AND CONTROL - WITH SPECIAL REFERENCE TO TRIALS IN THE FIELD OF ARRHYTHMIASAND SUDDEN-DEATH

The early termination of clinical trials, for either benefit or harm, often generates undue enthusiasm or alarm. The enhanced publicity atte nding early termination of a trial promotes inappropriate interpretati ons that are favored by the inherent difficulty of prompt and comprehe nsive data review. Furthermore, the process of monitoring the accumula ting outcome data for early evidence of treatment benefit or harm is f raught with many statistical and methodological difficulties. This rep ort from a task force convened by the Working Group on Arrhythmias of the European Society of Cardiology incorporates first, a series of tri als terminated appropriately or inappropriately for benefit or harm an d used as examples to illustrate the importance of suitable trial desi gn and of proper stopping rules; second, a description of the committe e structure of a clinical trial; third, an analysis of the general des ign issues; fourth, a review of the main issues in interim analysis wi th special reference to main strategies for reducing the rate of false -positive claims that could result from early trial termination; and f inally, a series of specific recommendations concerning the design, st ructure, analysis, interpretation, and presentation of a clinical tria l.