The first edition of Design and Analysis of Cross-Over Trials quickly became the standard reference on the subject and has remained so for more than 12 years. In that time, however, the use of cross-over trials has grown rapidly, particularly in the pharmaceutical arena, and researchers have made a number of advances in both the theory and methods applicable to these trials.
Completely revised and updated, the long-awaited second edition of this classic text retains its predecessor's careful balance of theory and practice while incorporating new approaches, more data sets, and a broader scope. Enhancements in the second edition include:
- A new chapter on bioequivalence
- Recently developed methods for analyzing longitudinal continuous and categorical data
- Real-world examples using the SAS system
- A comprehensive catalog of designs, datasets, and SAS programs available on a companion Web site at www.crcpress.com
The authors' exposition gives a clear, unified account of the design and analysis of cross-over trials from a statistical perspective along with their methodological underpinnings. With SAS programs and a thorough treatment of design issues, Design and Analysis of Cross-Over Trials, Second Edition sets a new standard for texts in this area and undoubtedly will be of direct practical value for years to come.
INTRODUCTION
What is a Cross-Over Trial?
With which Sort of Cross-Over Trial are We Concerned?
Why Do Cross-Over Trials Need Special Consideration?
A Brief History
Notation, Models and Analysis
Aims of this Book
Structure of the Book
THE 2 x 2 CROSS-OVER TRIAL
Introduction
Plotting the Data
The Analysis Using t-Tests
Sample Size Calculations
The Analysis of Variance
Aliasing of Effects
Consequences of preliminary testing
Analyzing the residuals
A Bayesian Analysis of the 2 x 2 Trial
The Use of Baseline Measurements
The Use of Covariates
Nonparametric Analysis
Binary Data
HIGHER-ORDER DESIGNS FOR TWO TREATMENTS
Introduction
’Optimal’ Designs
Balaam’s Design for Two Treatments
The Effect of Preliminary Testing in Balaam’s Design
Three-Period Designs with Two Sequences
Three-Period Designs with Four Sequences
A Three-Period Six-Sequence Design
Which Three-Period Design to Use?
Four-Period Designs with Two Sequences
Four-Period Designs with Four Sequences
Four-Period Designs with Six Sequences
Which Four-Period Design to Use?
Which Two-Treatment Design to Use?
DESIGNING CROSS-OVER TRIALS FOR THREE OR MORE TREATMENTS
Introduction
Variance-Balanced Designs
Optimality Results for Cross-Over Designs
Which Variance Balanced Design to Use?
Partially Balanced Designs
Comparing Test Treatments to a Control
Factorial Treatment Combinations
Extending the Simple Model for Carry-Over Effects
Computer Search Algorithms
ANALYSIS OF CONTINUOUS DATA
Introduction
The Fixed Subject Effects Model
The Random Subject Effects Model
Analyses for Higher-Order Two-Treatment Designs
The General Linear Mixed Model
Analysis of Repeated Measurements within Periods
Cross-Over Data as Repeated Measurements
Case Study: an Analysis of a Trial with Many Periods
ANALYSIS OF CATEGORICAL DATA
Introduction
Binary Data: Subject Effect Models
Binary Data: Marginal Models
Categorical Data
Further Topics
BIOEQUIVALENCE TRIALS
What is Bioequivalence
Testing for Average Bioequivalence
Power and Sample Size for ABE in the 2 x 2 Design
Individual Bioequivalence
Population Bioequivalence
ABE for a Replicate Design
Kullback–Leibler Divergence for Evaluating Bioequivalence
Modelling Pharmacokinetic Data
APPENDICES
Least Squares Estimation
SAS Code for Assessing ABEm IBE, and PBE in Replicate Cross-Over Trials
REFERENCES
