TITLE: Adaptive Designs for Clinical Trials and the ICH Guidance E20
SPEAKER: Christopher Jennison, University of Bath, Vladimir Dragalin, Johnson & Johnson, and Bruce W.Turnbull, Cornell University
MODERATOR: Bill Wang
Abstract:
The Draft ICH E20 Guideline lays down general principles for the conduct of adaptive designs. The scope of this Guideline is extensive, covering group sequential tests, adaptation using combination tests or the conditional error principle, trials that test multiple hypotheses, and adaptive designs that combine all these features.
In this tutorial, we shall start by reviewing the methods used to construct adaptive designs and giving examples of their application. We shall explain the five principles put forward in the Guideline and discuss their implications. We shall present topics that emerge from this discussion: the logistical challenges in implementing an adaptive design; the requirement for a trial to contribute to the wider drug development program, going beyond testing the null hypothesis of no treatment effect; implications of the Guidelines for the use of Bayesian methods; methods for producing unbiased estimates and computing confidence intervals on termination of an adaptive trial.
The session will conclude with a question-and-answer session.
Instructors’ Biography:
Christopher Jennison is Professor of Statistics at the University of Bath, UK. He was awarded his PhD from Cornell University for research into the sequential analysis of clinical trials and has continued to work in this area for the past 25 years. He has published extensively on group sequential methods and adaptive designs. His book with Professor Bruce Turnbull, “Group Sequential Methods with Applications to Clinical Trials”, is a standard text on this topic and is widely used by practising statisticians. Professor Jennison’s research is informed by experience of clinical trial analysis at the Dana Farber Cancer Institute, Boston and a broad range of consultancy with Medical Research institutes and Pharmaceutical companies in Europe, America and Asia. He has made numerous presentations at international conferences, in which he sets out to describe novel statistical methodology and its application to the design and analysis of clinical trials.
Dr. Vladimir Dragalin is a Vice President and Scientific Fellow at Janssen, Pharmaceutical Companies of Johnson and Johnson. He is adaptive designs expert with 25 years experience in developing the statistical methodology of adaptive designs, with over 12 years experience in pharmaceutical industry including positions at GlaxoSmithKline, Wyeth, Pfizer and at leading CROs Quintiles and Aptiv Solutions. Dr. Dragalin is a Fellow of the American Statistical Association and Member of the Drug Information Association, the Society for Clinical Trials, the International Society for CNS Clinical Trials and Methodology, and an Associate Editor of Journal of Biopharmaceutical Statistics. He is actively involved in the PhRMA Working Group on Adaptive Designs and the PhRMA Working Group on Adaptive Dose Ranging Studies (currently under DIA) and an elected member of the PhRMA Biostatistics and Data Management Technical Group.
Bruce Turnbull received the B.S. from Cambridge University in 1967 and the Ph.D. from Cornell University in 1971. After serving on the faculty at Stanford University and at the University of Oxford, he joined Cornell University in 1976, where he is currently Professor in the School of Operations Research and Information Engineering where he previously served as Acting Director.
From 2000–2002, he was founding Chairman of the newly formed Department of Statistical Science and currently also holds a professorial appointment there. In 1979 he was awarded the Snedecor Memorial Award by the American Statistical Association in recognition of his research.
He has authored over 130 publications and is the co-author of a book on statistical procedures for monitoring clinical trials. He has been a consultant to many organizations, including the Oak Ridge National Laboratory, Institute for Energy Analysis; and various pharmaceutical companies. Turnbull has served on the Board of Directors of the National Institute of Statistical Sciences, and on the Expert Review Panel for the National Toxicology Program Board of Scientific Counselors. He is on the Data and Safety Monitoring Committees for several major national and international clinical trials in the areas of cancer, heart disease, pulmonary disease and of AIDS sponsored by the National Institutes of Health and by the Veterans Administration. He has served on the editorial board of a number of statistical journals and is currently editor of the Chapman and Hall book series on biostatistics. He is a Fellow of the American Statistical Association and of the Royal Statistical Society.
Professor Turnbull also has emeritus status in the School of Operations Research and Information Engineering in Cornell’s College of Engineering.