TITLE: Clinical Trial Data Monitoring Committees and Reporting Statistical Centers: Problems and Solutions
SPEAKER: Susan Ellenberg, University of Pennsylvania, Matt Downs, MPH, Statistics Collaborative, Washington DC
Abstract: The number of clinical trials that are overseen by independent Data Monitoring Committees/Data and Safety Monitoring Boards is ever-increasing. A recent survey of DMC members showed that almost none had had training in DMC practices prior to their first time on a DMC, and most of those felt that such training would have been beneficial. Additionally, while many statistical centers and contract research organizations have substantial experience in developing DMC reports and presenting them at DMC meetings, many others are new to these processes; further, many DMC reports even from experienced centers are currently far from optimal. This course will be divided into 2 sections: first, we will cover the basics of DMC operations, including: typical responsibilities of DMCs; DMC composition; structure of DMC meetings; statistical aspects of data monitoring; and regulations and policies regarding operation of DMCs. We will also address ongoing and emerging issues about DMC operations, about which there is less current consensus. Points in the discussion will be illustrated with case studies. The second section of the course will address operational issues for statistical centers reporting to DMCs. This section will cover the basic responsibilities of the statistical center and describe best operational practices, with many examples of optimal reports.
Dr. Ellenberg’s research has focused on practical problems and ethical issues in designing, conducting and analyzing data from clinical trials, including surrogate endpoints, data monitoring committees, clinical trial designs, adverse event monitoring, vaccine safety and special issues in cancer and AIDS trials. At Penn, in addition to her teaching and administrative duties she serves as senior statistician for several multicenter clinical trials and directs the Biostatistics Core of the Penn Center for AIDS Research. She chairs the organizing committee for the annual Penn conference on statistical issues in clinical trials. She also served for many years as Associate Dean for Clinical Research, overseeing the human subjects protections programs, training and centralized research support of the Perelman School of Medicine.
Prior to her appointment at Penn, Dr. Ellenberg held positions of increasing responsibility in the federal government. From 1993 to 2004, she served as Director, Office of Biostatistics and Epidemiology in the Center for Biologics Evaluation and Research (CBER) at the U.S. Food and Drug Administration; prior to that she served as the first Chief of the Biostatistics Research Branch in the Division of AIDS, National Institute of Allergy and Infectious Diseases (1988-1993), and served in the Biometric Research Branch in the Cancer Therapy Evaluation Program, National Cancer Institute (1982-1988).
Dr. Ellenberg is a Fellow of the American Statistical Association, the Society for Clinical Trials and the American Association for the Advancement of Science, and is an elected member of the International Statistical Institute. She is the 2019 recipient of the Florence Nightingale David Award, a biannual award given jointly by the major North American statistical societies to a female statistician for outstanding achievements. The first edition of her book, Data Monitoring Committees in Clinical Trials: A Practical Perspective, co-authored with Drs. Thomas Fleming and David DeMets, was named Wiley Europe Statistics Book of the Year for 2002; a second edition was released in March 2019.
Matt Downs (MPH in Epidemiology and Biostatistics from the University of California, Berkeley) is a statistical scientist at Statistics Collaborative. Since 1999, he has served as the independent reporting statistician to DMCs for multinational Phase 2 and 3 trials in many disease areas. Mr. Downs speaks at professional meetings on a range of statistical topics, including dynamic allocation methods, conditional power, and implementation of treatment assignment algorithms. He is a member of the American Statistical Association and the Society for Clinical Trials.