Design and Analysis of Non-Inferiority Trials

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