In clinical trial practice, controversial statistical issues inevitably occur regardless of the compliance with good statistical practice and good clinical practice. But by identifying the causes of the issues and correcting them, the study objectives of clinical trials can be better achieved. Controversial Statistical Issues in Clinical Trials covers commonly encountered controversial statistical issues in clinical trials and, whenever possible, makes recommendations to resolve these problems.
The book focuses on issues occurring at various stages of clinical research and development, including early-phase clinical development (such as bioavailability/bioequivalence), bench-to-bedside translational research, and late-phase clinical development. Numerous examples illustrate the impact of these issues on the evaluation of the safety and efficacy of the test treatment under investigation. The author also offers recommendations regarding possible resolutions of the problems.
Written by one of the preeminent experts in the field, this book provides a useful desk reference and state-of-the art examination of problematic issues in clinical trials for scientists in the pharmaceutical industry, medical/statistical reviewers in government regulatory agencies, and researchers and students in academia.
Table of Contents
Introduction. Good Statistical Practices. Bench-to-Bedside Translational Research. Bioavailability and Bioequivalence. Hypotheses for Clinical Evaluation and Significant Digits. Instability of Sample Size Calculation. Integrity of Randomization/Blinding. Clinical Strategy for Endpoint Selection. Protocol Amendments. Seamless Adaptive Trial Designs. Multiplicity in Clinical Trials. Independence of Data Monitoring Committee. Two-Way ANOVA versus One-Way ANOVA with Repeated Measures. Validation of QOL Instruments. Missing Data Imputation. Center Grouping. Non-Inferiority Margin. QT Studies with Recording Replicates. Multiregional Clinical Trials. Dose Escalation Trials. Enrichment Process in Target Clinical Trials. Clinical Trial Simulation. Traditional Chinese Medicine. The Assessment of Follow-On Biologic Products. Generalizability/Reproducibility Probability. Good Review Practices. Probability of Success. References. Index.
Shein-Chung Chow, Ph.D., is a professor in the Department of Biostatistics and Bioinformatics at Duke University School of Medicine. Dr. Chow is also an adjunct professor of clinical sciences at Duke–National University of Singapore Graduate Medical School and the editor-in-chief of the Journal of Biopharmaceutical Statistics. He has authored or co-authored more than 200 papers and 19 books, including the recently published Handbook of Adaptive Designs in Pharmaceutical and Clinical Development. He earned his Ph.D. in statistics from the University of Wisconsin–Madison.
"… it is very valuable that the book calls the reader’s attention to the numerous problems which are relevant every day and I recommend to make this book available to personnel in all biometrical university departments, CROs and operating departments in the pharmaceutical industry to enable them to cope with the most important controversial aspects in planning and execution of clinical studies."
—Rainer Muche, ISCB News, December 2013
"This volume deals with an important area—issues in clinical trials research which are perhaps not fully resolved. … it is wide ranging, covering all aspects of clinical trials, and has excellent links and references to regulatory aspects. It will therefore provide a useful reference work for clinical trials researchers."
—David J. Hand, International Statistical Review, 2012
"I would recommend this book since it covers a number of areas that have not been covered in as much detail elsewhere. In particular, I thought the chapters on molecularly targeted therapies, follow-on biologics, multiregional clinical trials and good statistical practices were well written and useful."
—William Mietlowski, Journal of Biopharmaceutical Statistics, Issue 5, 2012
"Written by one of the preeminent experts in the field, this book provides a useful desk reference and state-of-the art examination of problematic issues in clinical trials for scientists in the pharmaceutical industry, medical/statistical reviewers in government regulatory agencies, and researchers and students in academia."