1st Edition

Design and Analysis of Non-Inferiority Trials

    454 Pages
    by Chapman & Hall

    454 Pages 8 B/W Illustrations
    by Chapman & Hall

    The increased use of non-inferiority analysis has been accompanied by a proliferation of research on the design and analysis of non-inferiority studies. Using examples from real clinical trials, Design and Analysis of Non-Inferiority Trials brings together this body of research and confronts the issues involved in the design of a non-inferiority trial. Each chapter begins with a non-technical introduction, making the text easily understood by those without prior knowledge of this type of trial.

    Topics covered include:

    • A variety of issues of non-inferiority trials, including multiple comparisons, missing data, analysis population, the use of safety margins, the internal consistency of non-inferiority inference, the use of surrogate endpoints, trial monitoring, and equivalence trials

    • Specific issues and analysis methods when the data are binary, continuous, and time-to-event

    • The history of non-inferiority trials and the design and conduct considerations for a non-inferiority trial

    • The strength of evidence of an efficacy finding and how to evaluate the effect size of an active control therapy

    A comprehensive discussion on the purpose and issues involved with non-inferiority trials, Design and Analysis of Non-inferiority Trials will assist current and future scientists and statisticians on the optimal design of non-inferiority trials and in assessing the quality of non-inferiority comparisons done in practice.

    What Is a Non-Inferiority Trial? Non-Inferiority Trial. Considerations. Strength of Evidence and Reproducibility. Evaluating the Active Control Effect. Across-Trials Analysis Methods. Three-Arm Non-Inferiority Trials. Multiple Comparisons. Missing Data and Analysis Sets. Safety Studies. Additional Topics. Inference on Proportions. Inferences on Means and Medians. Inference on Time-to-Event End Points. Appendix: Statistical Concepts. Index.


    Dr. Mark Rothmann earned his Ph. D. in Statistics at the University of Iowa. He taught several years as a professor and has worked at the U. S. Food and Drug Administration. He has done research in many areas involving the design and analysis of clinical trials.

    Dr. Brian L. Wiens, received his MS in statistics from Colorado State University and his Ph.D. in statistics from Temple University. He has worked at several pharmaceutical, biotechnology and medical device companies since 1991. He has published research in several areas of design and analysis of clinical trials. Dr. Wiens is a Fellow of the American Statistical Association.

    Dr. Ivan S.F. Chan received his M.S. in Statistics from The Chinese University of Hong Kong and his Ph.D. in Biostatistics from University of Minnesota. He has worked at Merck Research Laboratories since 1995 and is currently Senior Director and Franchise Head for vaccines, leading the statistical support for all vaccine clinical research programs at Merck. Dr. Chan has published research in many areas of statistics including exact inference, analysis of non-inferiority trials, and methodologies for clinical trials.

    "This important book is relevant because this type of trial is preferred when an approved treatment is available and a conventional placebo-controlled trial would be difficult to justify. These trials are complex and this book goes a long way toward helping the investigator with the issues that arise. … This book is comprehensive and includes extensive coverage of every topic. It includes both frequentist and Bayesian approaches as appropriate. Throughout every chapter, topics are fully explained and examples are completely worked out, including statistical formulas and results. … a modern and thorough compendium for anyone involved in the design and analysis of noninferiority trials."
    —Mark Bailey, Technometrics, November 2014

    "… it offers unique perspectives and insights from three renowned experts in clinical trials who work at the U.S. Food and Drug Administration (FDA) and in the pharmaceutical industry. It is refreshing to see FDA and industry perspectives blended thoughtfully, as in this book. … Written clearly and concisely, the book is a pleasure to read. Although there are some technical discussions intended for statisticians, most of the book is readily accessible to medical researchers with little statistical training. We recommend the book to anyone interested in NI trials—statisticians and nonstatisticians alike."
    —Zhiwei Zhang and Lei Nie, Journal of the American Statistical Association, March 2014

    "It is a pleasure to see a book completely devoted to the challenging arena of non-inferiority trials. … I am very impressed with its depth and breadth, and believe that it will be an important resource for anyone involved in designing non-inferiority trials. The authors weave in many examples, primarily in oncology, as well as a large set of references from the now substantial statistical literature on non-inferiority designs. … This book is a must-have resource for those involved in non-inferiority trials for the