Copyright © 1994 by the European Society of Cardiology.
© 1994 The European Society of Cardiology
The early termination of clinical trials: causes, consequences, and control
With special reference to trials in the field of arrhythmias and sudden death
TASK FORCE OF THE WORKING GROUP ON ARRHYTHMIAS OF THE EUROPEAN SOCIETY OF CARDIOLOGY*Correspondence: Peter J. Schwartz, MD, Professor of Medicine, Instituto di Clinica Medica Generale e Terapia Medica, Universita' degli Studi di milano, Via F. Sforza, 35, 20122 Milano, Italy.
Abstract
*This paper summarizes the outcome of a workshop proposed by Peter J. Schwartz and held in Ile de Porquerolles, France, 24-26 June 1993. It was organized by the Working Group on Arrhythmias of the European Society of Cardiology, and its funding administered by the European Society of Cardiology. The workshop was chaired by Peter J. Schwartz and co-chaired by Curt Furberg and Desmond G. Julian. Participating in the workshop and co-authoring the paper were J. Thomas Bigger Jr. (New York, U.S.A.); Gunter Breithardt (Munster, Germany); A. John Camm (London, U.K.); David L. DeMets (Madison, U.S.A.); Curt D. Furberg (Winston-Salem, U.S.A.); Alfred Hallstrom (Seattle, U.S.A.); Michiel J. Janse (Amsterdam, The Netherlands); Desmond G. Julian (London, U.K.); Kuang-Kuo Gordon Lan (Rockville, U.S A.), Ralph Lazzara (Oklahoma City, U.S.A.); Frank I. Marcus (Tucson, U S.A.), Arthur J. Moss (Rochester, U.S.A.); Peter J. Schwartz (Pavia, Italy); Jan G.P. Tijssen (Amsterdam, The Netherlands); Albert L. Waldo (Cleveland, U.S A.). Not attending but acting as advisor was Stuart J. Pocock (London, U.K.). The final preparation and organization of the manuscript were the responsibility of A. John Camm, Desmond G. Julian, Peter J. Schwartz, and Jan G.P. Tijssen.
The early termination of clinical trials, for either benefit or harm, often generates undue enthusiasm or alarm. The enhanced publicity attending early termination of a trial promotes inappropriate interpretations because of the inherent difficulty of a prompt and comprehensive data review. Furthermore, the process of monitoring the accumulating outcome data for early evidence of treatment benefit or harm is fraught with many statistical and methodological difficulties. This report from a Task Force convened by the Working Group on Arrhythmias of the European Society of Cardiology incorporates first, a series of trials terminated appropriately or inappropriately for benefit or harm and used as examples to illustrate the importance of suitable trial design and of proper stopping rules; second, a description of the committee structure of a clinical trial; third, an analysis of the general design issues; fourth, a review of the main issues in interim analysis with special reference to main strategies for reducing the rate of false-positive claims that could result from early trial termination; and finally, a series of specific recommendations concerning the design, structure, analysis, interpretation, and presentation of a clinical trial.
Key Words: Antiarrhythmic drugs • cardiac mortality • interim analysis