Since 1945, "The Annual Deming Conference on Applied Statistics" has been an important event in the statistics profession. In Clinical Trial Biostatistics and Biopharmaceutical Applications, prominent speakers from past Deming conferences present novel biostatistical methodologies in clinical trials as well as up-to-date biostatistical applications from the pharmaceutical industry. Divided into five sections, the book begins with emerging issues in clinical trial design and analysis, including the roles of modeling and simulation, the pros and cons of randomization procedures, the design of Phase II dose-ranging trials, thorough QT/QTc clinical trials, and assay sensitivity and the constancy assumption in noninferiority trials. The second section examines adaptive designs in drug development, discusses the consequences of group-sequential and adaptive designs, and illustrates group sequential design in R. The third section focuses on oncology clinical trials, covering competing risks, escalation with overdose control (EWOC) dose finding, and interval-censored time-to-event data.In the fourth section, the book describes multiple test problems with applications to adaptive designs, graphical approaches to multiple testing, the estimation of simultaneous confidence intervals for multiple comparisons, and weighted parametric multiple testing methods. The final section discusses the statistical analysis of biomarkers from omics technologies, biomarker strategies applicable to clinical development, and the statistical evaluation of surrogate endpoints. This book clarifies important issues when designing and analyzing clinical trials, including several misunderstood and unresolved challenges. It will help readers choose the right method for their biostatistical application. Each chapter is self-contained with references.

Emerging Issues in Clinical Trial Design and Analysis Emerging Challenges of Clinical Trial Methodologies in Regulatory Applications H.M. James Hung and Sue-Jane Wang Review of RandomizationMethods in Clinical Trials Vance W. Berger and William C. Grant First Dose Ranging Clinical Trial Design: More Doses? Or a Wider Range? Guojun Yuan and Naitee Ting Thorough QT/QTc Clinical Trials Yi Tsong Controversial (Unresolved) Issues in Noninferiority Trials Brian L. Wiens Adaptive Clinical Trials Adaptive Designs in Drug Development Sue-Jane Wang and H.M. James Hung Optimizing Group-Sequential Designs with Focus on Adaptability: Implications of Nonproportional Hazards in Clinical Trials Edward Lakatos Group Sequential Design in R Keaven M. Anderson Clinical Trials in Oncology Issues in the Design and Analysis of Oncology Clinical Trials Stephanie Green Competing Risks and Their Applications in Cancer Clinical Trials Chen Hu, James J. Dignam, and Ding-Geng (Din) Chen Dose Finding with Escalation with Overdose Control in Cancer Clinical Trials Andre Rogatko and Mourad Tighiouart Interval-Censored Time-to-Event Data and Their Applications in Clinical Trials Ling Ma, Yanqin Feng, Ding-Geng (Din) Chen, and Jianguo Sun Multiple Comparisons in Clinical Trials Introduction to Multiple Test Problems, with Applications to Adaptive Designs Jeff Maca, Frank Bretz, and Willi Maurer Graphical Approaches to Multiple Testing Frank Bretz, Willi Maurer, and Jeff Maca Pairwise Comparisons with Binary Responses: Multiplicity-Adjusted P-Values and Simultaneous Confidence Intervals Bernhard Klingenberg and Faraz Rahman Comparative Study of FiveWeighted Parametric Multiple Testing Methods for Correlated Multiple Endpoints in Clinical Trials Changchun Xie, Xuewen Lu, and Ding-Geng (Din) Chen Clinical Trials in the Genomic Era Statistical Analysis of Biomarkers from Omics Technologies Herbert Pang and Hongyu Zhao Understanding Therapeutic Pathways via Biomarkers and Other Uses of Biomarkers in Clinical Studies Michael D. Hale and Scott D. Patterson Statistical Evaluation of Surrogate Endpoints in Clinical Studies Geert Molenberghs, Ariel Alonso Abad, Wim Van der Elst, Tomasz Burzykowski, and Marc Buyse Index