Classical and Adaptive Clinical Trial Designs Using ExpDesign Studio

Mark Chang

• Publisher: Wiley-Interscience
• Year: 2010
• Print ISBN:
  9780470276129
• eBook ISBN:
  9780470438565
• Edition: 1
• Topic: Medicine
• Subtopic: Pharmacology

ExpDesign Studio facilitates more efficient clinical trial design

This book introduces pharmaceutical statisticians, scientists, researchers, and others to ExpDesign Studio software for classical and adaptive designs of clinical trials. It includes the Professional Version 5.0 of ExpDesign Studio software that frees pharmaceutical professionals to focus on drug development and related challenges while the software handles the essential calculations and computations. After a hands-on introduction to the software and an overview of clinical trial designs encompassing numerous variations, Classical and Adaptive Clinical Trial Designs Using ExpDesign Studio:

• Covers both classical and adaptive clinical trial designs, monitoring, and analyses
• Explains various classical and adaptive designs including groupsequential, sample-size reestimation, dropping-loser, biomarker-adaptive, and response-adaptive randomization designs
• Includes instructions for over 100 design methods that have been implemented in ExpDesign Studio and step-by-step demos as well as real-world examples
• Emphasizes applications, yet covers key mathematical formulations
• Introduces readers to additional toolkits in ExpDesign Studio that help in designing, monitoring, and analyzing trials, such as the adaptive monitor, graphical calculator, the probability calculator, the confidence interval calculator, and more
• Presents comprehensive technique notes for sample-size calculation methods, grouped by the number of arms, the trial endpoint, and the analysis basis

Written with practitioners in mind, this is an ideal self-study guide for not only statisticians, but also scientists, researchers, and professionals in the pharmaceutical industry, contract research organizations (CROs), and regulatory bodies. It's also a go-to reference for biostatisticians, pharmacokinetic specialists, and principal investigators involved in clinical trials.

ERRATUM
Classical and Adaptive Clinical Trial Designs Using ExpDesign Studio
By Mark Chang

The license for the ExpDesign Studio software on the CD included with this book is good for one-year after installation of the software. Prior to the expiration of this period, the software will generate a reminder about renewal for the license. The user should contact CTriSoft International (the owners of ExpDesign Studio) at www.CTriSoft.net or by email at [email protected], about renewal for the license.

This should have been made clear in the first printing of this book. We apologize for this error.

Chapter 1

ExpDesign Studio

1.1 INTRODUCTION

ExpDesign Studio (ExpDesign) is an integrated environment for designing experiments or clinical trials. It is a powerful and user-friendly statistical software product that has seven integrated main components: classical design (CD), sequential design (SD), multistage design (MSD), dose-escalation design (DED), adaptive design (AD), adaptive trial monitoring (ATM), and dose-escalation trial monitoring (DTM) modules. In addition, the ExpDesign randomizor can generate random variates from a variety of distributions. The ExpDesign toolkit provides features for distributional calculation, confidence intervals, and function and data plotting (Figure 1.1).

Figure 1.1 ExpDesign integrated environment.

Classical trials are the most commonly used in practice. ExpDesign provides nearly 150 methods for sample-size calculations in CD for different trial designs. It includes methods for single-, two-, and multiple-group designs, and for superiority, noninferiority, and equivalence designs with various endpoints. See the list of classical design methods in Appendix B.

Group sequential trials are advanced designs with multiple analyses. A group sequential trial is usually a cost-effective design compared to a classical design. SD covers a broad range of sequential trials with different endpoints and different types of stopping boundaries.

A multistage design is an exact method for group sequential trials with a binary response, whereas group sequential design uses an asymptotic approach. MSD provides three optimal designs among others: MinMax, MinExp, and MaxUtility, which minimize the maximum sample size, minimize the expected sample size, and maximize the utility index, respectively.

A dose-escalation trial in aggressive disease areas such as oncology has unique characteristics. Due to the toxicity of the testing drug, researchers are allowed to use fewer patients to obtain as much information as possible about the toxicity profile or maximum tolerable dose. By means of computer simulations, DED provides researchers with an efficient way to search for an optimal design for dose-escalation trials with a variety of criteria. It includes traditional escalation rules, restricted escalation rules, two-stage scalation algorithms, and the Bayesian continual reassessment method (CRM).

AD in ExpDesign Studio allows you to design and simulate various adaptive trial, such as sample-size reestimation, dropping a loser, response-adaptive randomization, and biomarker-adaptive designs. You can use response-adaptive randomization to assign more patients to superior treatment groups or to drop a “loser” or inferior group. You may stop a trial prematurely to claim efficacy or futility based on the data observed. You may modify the sample size based on the treatment difference observed. All design reports are generated through an automation procedure that has built-in knowledge of statistical experts in a clinical trial.

ATM and DTM assist in monitoring an ongoing trial. They inform the user if the stopping boundary has been crossed and will also generate interim results such as conditional power, new sample size required, and dynamic random...

Table of contents

• Cover
• Half Title page
• Title page
• Copyright page
• Preface
• Self-Study and Practice Guide
• Chapter 1: ExpDesign Studio
• Chapter 2: Clinical Trial Design
• Chapter 3: Classical Trial Design
• Chapter 4: Group Sequential Trial Design
• Chapter 5: Adaptive Trial Design
• Chapter 6: Adaptive Trial Monitoring
• Chapter 7: Oncology Adaptive Trial Design
• Chapter 8: Adaptive Trial Simulator
• Chapter 9: Further Assistance From ExpDesign Studio
• Chapter 10: Classical Design Method Reference
• Appendix A: Validation of ExpDesign Studio
• Appendix B: Sample-Size Calculation Methods: Classical Design
• References
• Index
• System Requirements, Software Installation, and Software License Agreement