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Design and Analysis of Non-Inferiority Trials

By Mark D. Rothmann, Brian L. Wiens, Ivan S.F. Chan

Chapman and Hall/CRC – 2011 – 454 pages

Series: Chapman & Hall/CRC Biostatistics Series

Purchasing Options:

  • Add to CartHardback: $98.95
    978-1-58488-804-8
    July 11th 2011

Description

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.

Reviews

"… 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 pharmaceutical industry, and a must-read for those new to non-inferiority trials. A portion of a special topics course in a biostatistics department could be built around this book, and this exposure would be especially valuable for students considering a career in or around the pharmaceutical industry."

—Erica Brittain, Australian & New Zealand Journal of Statistics, May 2012

"This is the first book which is devoted solely to non-inferiority studies. All three authors have published several papers on that topic over the last years. This comprehensive book covers in more than 400 pages nearly all aspects about non-inferiority trials, and beyond. It is also an excellent source of references about non-inferiority studies. … recommended for anyone working with clinical trials and in particular for those working in late phase drug development. It is an excellent source of concepts and statistical methods relevant for biostatisticians, clinical epidemiologists and students. This book also is a good source for non-inferiority studies for scientists from the clinical field."

—Steffen Witte, Journal of Biopharmaceutical Statistics, 2012

Contents

What Is a Non-Inferiority Trial?

Definition of Non-Inferiority

Reasons for Non-Inferiority Trials

Different Types of Comparisons

A History of Non-Inferiority Trials

References

Non-Inferiority Trial Considerations

Introduction

External Validity and Assay Sensitivity

Critical Steps and Issues

Sizing a Study

Example of Anti-Infectives

References

Strength of Evidence and Reproducibility

Introduction

Strength of Evidence

Reproducibility

References

Evaluating the Active Control Effect

Introduction

Active Control Effect

Meta-Analysis Methods

Bayesian Meta-Analyses

References

Across-Trials Analysis Methods

Introduction

Two Confidence Interval Approaches

Synthesis Methods

Comparing Analysis Methods and Type I Error Rates

A Case in Oncology

References

Three-Arm Non-Inferiority Trials

Introduction

Comparisons to Concurrent Controls

Bayesian Analyses

References

Multiple Comparisons

Introduction

Comparing Multiple Groups to an Active Control

Non-Inferiority on Multiple End Points

Testing for Both Superiority and Non-Inferiority

References

Missing Data and Analysis Sets

Introduction

Missing Data

Analysis Sets

References

Safety Studies

Introduction

Considerations for Safety Study

Cardiovascular Risk in Antidiabetic Therapy

References

Additional Topics

Introduction

Interaction Tests

Surrogate End Points

Adaptive Designs

Equivalence Comparisons

References

Inference on Proportions

Introduction

Fixed Thresholds on Differences

Fixed Thresholds on Ratios

Fixed Thresholds on Odds Ratios

Bayesian Methods

Stratified and Adjusted Analyses

Variable Margins

Matched-Pair Designs

References

Inferences on Means and Medians

Introduction

Fixed Thresholds on Differences of Means

Fixed Thresholds on Ratios of Means

Analyses Involving Medians

Ordinal Data

References

Inference on Time-to-Event End Points

Introduction

Censoring

Exponential Distributions

Nonparametric Inference Based on a Hazard Ratio

Analyses Based on Landmarks and Medians

Comparisons Over Preset Intervals

References

Appendix: Statistical Concepts

Frequentist Methods

Bayesian Methods

Comparison of Methods

Stratified and Adjusted Analyses

References

Index

Author Bio

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.

Name: Design and Analysis of Non-Inferiority Trials (Hardback)Chapman and Hall/CRC 
Description: By Mark D. Rothmann, Brian L. Wiens, Ivan S.F. Chan. 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...
Categories: Statistics for the Biological Sciences, Clinical Implementation