Bayesian Methods in Pharmaceutical Research

Since the early 2000s, there has been increasing interest within the pharmaceutical industry in the application of Bayesian methods at various stages of the research, development, manufacturing, and health economic evaluation of new health care interventions. In 2010, the first Applied Bayesian Biostatistics conference was held, with the primary objective to stimulate the practical implementation of Bayesian statistics, and to promote the added-value for accelerating the discovery and the delivery of new cures to patients. This book is a synthesis of the conferences and debates, providing an overview of Bayesian methods applied to nearly all stages of research and development, from early discovery to portfolio management. It highlights the value associated with sharing a vision with the regulatory authorities, academia, and pharmaceutical industry, with a view to setting up a common strategy for the appropriate use of Bayesian statistics for the benefit of patients. The book covers: Theory, methods, applications, and computing Bayesian biostatistics for clinical innovative designs Adding value with Real World Evidence Opportunities for rare, orphan diseases, and pediatric development Applied Bayesian biostatistics in manufacturing Decision making and Portfolio management Regulatory perspective and public health policies Statisticians and data scientists involved in the research, development, and approval of new cures will be inspired by the possible applications of Bayesian methods covered in the book. The methods, applications, and computational guidance will enable the reader to apply Bayesian methods in their own pharmaceutical research.

I Introductory Part Chapter 1: Bayesian Background Emmanuel Lesaffre and Gianluca Baio Chapter 2: FDA Regulatory Acceptance of Bayesian StatisticsGregory Campbell Chapter 3: Bayesian Tail Probabilities for Decision Making Leonhard Held II Clinical Development Chapter 4: Clinical Development in the Light of Bayesian Statistics David Ohlssen Chapter 5: Prior ElicitationNicky Best, Nigel Dallow, and Timothy Montague Chapter 6: Use of Historical Data Beat Neuenschwander and Heinz Schmidli Chapter 7: Dose Ranging Studies and Dose Determination Phil Woodward, Alun Bedding, and David Dejardin Chapter 8: Bayesian Adaptive Designs in Drug Development Gary L. Rosner Chapter 9: Bayesian Methods for Longitudinal Data with MissingnessMichael J. Daniels and Dandan Xu Chapter 10: Survival Analysis and Censored Data Linda D. Sharples and Nikolaos Demiris Chapter 11: Benefit of Bayesian Clustering of Longitudinal Data: Study of Cognitive Decline for Precision Medicine Anais Rouanet, Sylvia Richardson, and Brian Tom Chapter 12: Bayesian Frameworks for Rare Disease Clinical Development Programs Freda Cooner, Forrest Williamson, and Bradley P. Carlin Chapter 13: Bayesian Hierarchical Models for Data Extrapolation and Analysis in Pediatric Disease Clinical Trials Cynthia Basu and Bradley P. Carlin III Post-Marketing Chapter 14: Bayesian Methods for Meta-AnalysisNicky J Welton, Haley E Jones, and Sofia Dias Chapter 15: Economic Evaluation and Cost-Effectiveness of Health Care InterventionsNicky J Welton, Mark Strong, Christopher Jackson, and Gianluca Baio Chapter 16: Bayesian Modeling for Economic Evaluation Using "Real World Evidence"Gianluca Baio Chapter 17: Bayesian Benefit-Risk Evaluation in Pharmaceutical Research Carl Di Casoli, Yueqin Zhao, Yannis Jemiai, Pritibha Singh, and Maria Costa IV Product Development and Manufacturing Chapter 18: Product Development and Manufacturing Bruno Boulanger and Timothy Mutsvari Chapter 19: Process Development and Validation John J. Peterson Chapter 20: Analytical Method and Assay Pierre Lebrun and Eric Rozet Chapter 21: Bayesian Methods for the Design and Analysis of Stability Studies Tonakpon Hermane Avohou, Pierre Lebrun, Eric Rozet, and Bruno Boulanger Chapter 22: Content Uniformity Testing Steven Novick and Buffy Hudson-Curtis Chapter 23: Bayesian methods for in vitro dissolution drug testing and similarity comparisons Linas Mockus and Dave LeBlond Chapter 24: Bayesian Statistics for Manufacturing Tara Scherder and Katherine Giacoletti V Additional Topics Chapter 25: Bayesian Statistical Methodology in the Medical Device Industry Tarek Haddad Chapter 26: Program and Portfolio Decision-Making Nitin Patel, Charles Liu, Masanori Ito, Yannis Jemiai, Suresh Ankolekar, and Yusuke Yamaguchi

Emmanuel Lesaffre Emmanuel Lesaffre studied mathematics at the University of Antwerp and received his PhD in statistics at the University of Leuven, Belgium. He is full professor at L-Biostat, KU Leuven, and part-time professor at University of Hasselt. He had a joint position at Erasmus University in Rotterdam, the Netherlands from 2007 to 2014. His statistical research is rooted in medical research questions. He has worked in a great variety of medical research areas, but especially in oral health, cardiology, nursing research, ophthalmology and oncology. He also contributed on various statistical topics, i.e. discriminant analysis, hierarchical models, model diagnostics, interval-censored data, misclassification issues, variable selection, various clinical trial topics and diagnostic tests both under the frequentist and Bayesian paradigm. He has taught introductory and advanced courses to medical and statistical researchers. In the last two decades, his research focused on Bayesian techniques resulting in a textbook and courses taught at several universities and governmental organizations. Recently, he co-authored a textbook on interval censoring. In total he (co)-authored nine books and more than 600 papers. He has served as statistical consultant on a great variety of clinical trials in various ways, e.g. as a steering committee and data-monitoring committee member. He is the founding chair of the Statistical Modelling Society (2002) and was ISCB president (2006-2008). Further, he is ASA and ISI fellow and honorary member of the Society for Clinical Biostatistics and of the Statistical Modelling Society. He has been involved in the organisation of the Bayes 20XX conference since 2013. Gianluca Baio Gianluca Baio is a Professor of Statistics and Health Economics in the Department of Statistical Science at University College London. He graduated in Statistics and Economics from the University of Florence (Italy). He then completed a PhD programme in Applied Statistics again at the University of Florence, after a period at the Program on the Pharmaceutical Industry at the MIT Sloan School of Management, Cambridge (USA). I then worked as a Research Fellow and then Lecturer in the Department of Statistical Sciences at University College London (UK). His main interests are in Bayesian statistical modelling for cost effectiveness analysis and decision-making problems in the health systems, hierarchical/multilevel models and causal inference using the decision-theoretic approach. He also leads the Statistics for Health Economic Evaluation research group within the department of Statistical Science, whose activity revolves around the development and application of Bayesian statistical methodology for health economic evaluation, e.g. cost-effectiveness or cost-utility analysis. He also collaborates with the UK National Institute for Health and Care Excellence (NICE) as a Scientific Advisor on Health Technology Appraisal projects and has served as Secretary (2014-2016) and then Programme Chair (2016-2018) in the Section on Biostatistics and Pharmaceutical Statistics of the International Society for Bayesian Analysis. He has been involved in the organisation of the Bayes 20XX conference since 2013. Bruno Boulanger Bruno Boulanger, Ph.D. Organization: PharmaLex Belgium Dr Bruno Boulanger, Chief Scientific Officer, PharmaLex Belgium Belgium Lecturer, School of Pharmacy, Université de Liège, Belgium After a post-doctorate at the Université Catholique de Louvain (Belgium) and the University of Minnesota (USA) in Statistics applied to simulation of clinical trials, Bruno joined Eli Lilly in Belgium in 1992. Bruno holds various positions in Europe and in the USA where he gathered experience in several areas of pharmaceutical industry including discovery, toxicology, CMC and early clinical phases. Bruno joined UCB Pharma in 2007 as Director of Exploratory Statistics, contributing the implementation of Model-Based Drug Development strategy and applied Bayesian statistics. Bruno is also since 2000 Lecturer at the Université of Liège, in the School of Pharmacy, teaching Design of Experiments and Statistics. Bruno organizes and contributes since 1998 to Non-Clinical Statistics Conference in Europe and setup in 2010 the Applied Bayesian Biostatistics conference. Bruno is also a USP Expert, member of the Committee of Experts in Statistics since 2010. Bruno has authored or co-authored more than 100 publications in applied statistics.