TITLE: Group Sequential and Adaptive Methods for Clinical Trials
INSTRUCTOR: Christopher Jennison, University of Bath and Bruce Turnbull, Cornell University
MODERATOR: Bill Wang
Abstract:
In the first part of this course we shall review group sequential designs, in particular, error spending tests that can handle unpredictable levels of information at each analysis. We shall discuss more recent developments in: accommodating delayed observations (“pipeline” data) at interim analyses; trials with multiple arms or multiple endpoints; controlling bias when reporting results of a trial with early stopping. Statistical software will be used to illustrate the methods and examples.
The course will then move on to adaptive designs based on combination tests or the conditional error principle, and combining these methods with closed testing procedures to create adaptive designs that test multiple hypotheses while controlling the family-wise error rate. We shall discuss applications including sample size re-estimation, Phase II/III seamless designs, multi-arm multi-stage designs, and enrichment designs. Adaptations may follow rigid rules that are pre-specified in the protocol or a more flexible approach may be followed with the possibility of unplanned changes at interim analyses. The complexity and flexibility of an adaptive design has implications for the inferences that can be draw on its conclusion: we shall explain what is achievable using current methods and note areas where further work is needed.
Participants will be invited to discuss their experiences in implementing adaptive designs, interacting with regulators, or serving on Data and Safety Monitoring Boards.
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.
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.