 |
 |
DATA MONITORING IN CLINICAL TRIALS Royal Statistical Society Medical Section / Merseyside Local Group Tuesday 31st January 2006 2pm-5pm Thompson Yates Lecture Theatre, Thompson Yates Building, University of Liverpool Please contact Catrin Tudur Smith ([log in to unmask]) to register a place Stuart Pocock (London School of Hygiene and Tropical Medicine) Current Controversies in Data Monitoring This talk will cover a range of controversial issues concerning Data Monitoring Committees (DMCs) and statistical stopping guidelines in clinical trials: 1) What constitutes a sensible statistical stopping boundary for claiming benefit of a new treatment. 2) Some challenging examples of trials where DMCs decision to stop (or not) has a major bearing on future clinical practice. 3) Sample size re-estimation, including the controversial adaptive designs whereby unblinded interim data are used to determine eventual trial size. 4) Organizational matters in DMC conduct, such as when to stay blinded, interactions with sponsors and the role of independent statistician. 5) The ethical dilemmas in trial data monitoring, balancing the responsibilities to patients in a trial, society's need for convincing evidence of therapeutic progress, and the dangers of stopping a trial too soon. Tony Johnson (MRC Biostatistics Unit, University of Cambridge Institute of Public Health) Trial Steering Committees, Trial Management Groups, Data Monitoring Committees: What do they do in the Management of Clinical Trials? The conduct of clinical trials in UK now requires the setting-up of a formidable management structure to safeguard their integrity without exposing patients to unwarranted risk of adverse events. Despite the publication of guidelines on research governance and trial management there are several models being used by different funding agencies and some confusion about the way in which the separate committees operate, communicate, and interlink. Such confusion can result in problems that are easily avoidable as will be illustrated with examples that have arisen in recent studies. Some suggestions for the operation of these committees will be made based on experience of clinical trials in psychiatry, epilepsy, and transfusion medicine. Matt Sydes, on behalf of the DAMOCLES group (MRC Clinical Trials Unit) Damocles: Issues In Data Monitoring For Randomised Controlled Trials DAMOCLES was a multi-method study conducted in 2001-2003. Systematic reviews, surveys and interviews were used to investigate how Data Monitoring Committees (DMCs) for randomised controlled trials (RCTs) are utilized and organised, how they make decisions, and how the quality of decision-making of DMCs could be improved. The results indicated that a variety of processes and procedures are employed, and that coherent guidance is not easily available for many issues relating to DMCs; in some cases, there is no clear consensus on how contentious issues ought to be addressed. The research findings(1) informed the development of a template for a Charter for DMCs(2). This provides a structure to outline the roles, remit and organisation of a DMC throughout the trial. The Charter is to be completed by the trial investigators together with the DMC members prior to the start of the trial. Data monitoring issues are addressed systematically and transparently, together with justification, advice and illustrative examples. The Charter forms a logical framework allowing the DMC and investigators to cover both general DMC issues and aspects of data monitoring which are often neglected. Several RCTs are now beginning to use this Charter and finding it helpful. It is envisaged that more widespread adoption will help DMCs and investigators to address many aspects of DMC functioning more consistently, effectively and efficiently. (1) AM Grant, DG Altman, A. B. Babiker, MK Campbell, FJ Clemens, JH Darbyshire, DR Elbourne, SK McLeer, MKB Parmar, SJ Pocock, DJ, Spiegelhalter, MR Sydes, AE Walker, SA Wallace, and and the DAMOCLES group. Issues in data monitoring and interim analysis of trials. Health Technology Assessment monograph series 9 (7), 2005. (2) DAMOCLES study group. A proposed charter for clinical trial Data Monitoring Committees: helping them to do their job well. The Lancet 365:711-722, 2005. --------------------------------------------------- Dr. Catrin Tudur Smith Lecturer in Medical Statistics Centre for Medical Statistics and Health Evaluation School of Health Sciences University of Liverpool Shelley's Cottage Brownlow Street L69 3GS ---------------------------------------------------