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Introduction to Randomized Controlled Clinical Trials, Second Edition

By John N.S. Matthews

Series Editor: Chris Chatfield, Martin A. Tanner, Bradley. P. Carlin, Martin A. Tanner

Chapman and Hall/CRC – 2006 – 304 pages

Series: Chapman & Hall/CRC Texts in Statistical Science

Purchasing Options:

  • Add to CartPaperback: $73.95
    978-1-58488-624-2
    June 26th 2006

Description

Evidence from randomized controlled clinical trials is widely accepted as the only sound basis for assessing the efficacy of new medical treatments. Statistical methods play a key role in all stages of these trials, including their justification, design, and analysis. This second edition of Introduction to Randomized Controlled Clinical Trials provides a concise presentation of the principles applied in this area. It details the concepts behind randomization and methods for designing and analyzing trials and also includes information on meta-analysis and specialized designs, such as cross-over trials, cluster-randomized designs, and equivalence studies.

This latest edition features new and revised references, examples, exercises, and a new chapter dedicated to binary outcomes and survival analysis. It also presents numerous examples taken from the medical literature, contains exercises at the end of each chapter, and offers solutions in an appendix. The author uses Minitab and R software throughout the text for implementing the methods that are presented.

Comprehensive and accessible, Introduction to Randomized Controlled Clinical Trials is well-suited for those familiar with elementary statistical ideas and methods who want to further their knowledge of the subject.

Reviews

"…this book is very well presented and … is extremely pleasant and enjoyable to read. Both the statistical concepts and medical examples are very well explained. I highly recommend this book as a course text and as an excellent reference book for anyone interested in clinical trials. A copy of it should certainly appear in every university library."

Journal of Applied Statistics, 2007

"…a very welcome revision. The author has drawn upon his experiences to provide a valuable account of the important statistical underpinnings of the randomized clinical trial. … written primarily for students of statistics … highly desirable … ideal for its intended audience."

—Susan Todd, The University of Reading, UK

"…The second edition builds upon the first by adding a chapter on binary and survival data and updating the chapter on balancing treatment allocations. Whether you might need to introduce a novice to the unique principles and pitfalls of clinical trials or remind an experienced statistician of their importance, this book would serve your purpose admirably. Moreover, as an experienced clinical trialist, I found it to be an excellent reminder of the statistical principles and concepts that underlie the day-to-day rules of our profession. … Throughout, the author discusses principles, concepts and applications with a clarity that will be truly appreciated by those trained in mathematics. Each chapter focuses on a key challenge in the analysis of clinical trials and its associated statistical implications. … Overall, the choice of chapter topics is comprehensive and well chosen. … This text is definitely a handy reference-certainly worthwhile for a statistically conversant audience who are lacking in clinical trials experience. Such an audience will find this book educational and the author's concise style, an easy read. I would definitely recommend it for the bookshelf of anyone working in clinical trials."

—Karen Kesler, Journal of Biopharmaceutical Statistics, Issue 5, 2007

Contents

WHAT IS A RANDOMIZED CONTROLLED TRIAL?

Definition and Key Features

Historical Context and the Nature of RCTS

Structure and Justification of RCTs

Exercises

BIAS

What is meant by bias in RCTs?

Types of Bias

Exercises

HOW MANY PATIENTS DO I NEED?

Criteria for Sample Size Calculations

Hypothesis Tests

Sample Size for a Normally Distributed Variable

Sample Size for a Binary Variable

General Remarks About Sample Size Calculations

Exercises

METHODS OF ALLOCATION

Simple Randomization

Random Permuted Blocks

Biased Coin Designs and Urn Schemes

Unequal Randomization

Stratification

Minimization

Exercises

ASSESSMENT, BLINDING AND PLACEBOS

Double and Single Blindness

Placebos

Practical Considerations

Exercises

ANALYSIS OF RESULTS

Example

Use of Confidence Intervals

Baselines: Uses and Abuses

Analysis of Covariance

Exercises

FURTHER ANALYSIS: BINARY AND SURVIVAL DATA

Binary Data: An Example and a Statistical Model

Point Estimates and Hypothesis Tests

Interval Estimates for the Binary Case

Adjusting Binary Outcomes for Baseline Observations

Survival Analysis

Analyses Using Randomization Models

Exercises

MONITORING ACCUMULATING DATA

Motivation and Problems with Repeated Analysis of Data

Sequential and Group-Sequential Methods

Other Approaches to Accumulating Data

Data Monitoring Committees

Exercises

SUBGROUPS AND MULTIPLE OUTCOMES

The Role of Sub-groups in Randomized Clinical Trials

Methods for Comparing Sub-groups

Methods of Selecting Sub-groups

Qualitative Interactions

Multiple outcomes

Correction of P-values

Some Alternative Methods for Multiple Outcomes

Exercises

PROTOCOLS AND PROTOCOL DEVIATIONS

Protocols: Their Nature and Role

Protocol Deviation

Analysis by Intention-to-Treat

Exercises

SOME SPECIAL DESIGNS: CROSSOVERS, EQUIVALENCE AND CLUSTERS

Crossover Trials and Parallel Group Trials

The AB/BA Design

Analysis of AB/BA Design for Continuous Outcomes

The Issue of Carryover

Equivalence Trials

Cluster Randomized Trials

Exercises

META-ANALYSES OF CLINICAL TRIALS

What Are Meta-Analyses and Why Are They Needed?

Some Methodology for Meta-Analysis

Some Graphical Methods for Meta-Analysis

Some General Issues in Meta-Analysis

Exercises

FURTHER READING

SOLUTIONS TO EXERCISES

REFERENCES

Name: Introduction to Randomized Controlled Clinical Trials, Second Edition (Paperback)Chapman and Hall/CRC 
Description: By John N.S. MatthewsSeries Editor: Chris Chatfield, Martin A. Tanner, Bradley. P. Carlin, Martin A. Tanner. Evidence from randomized controlled clinical trials is widely accepted as the only sound basis for assessing the efficacy of new medical treatments. Statistical methods play a key role in all stages of these trials, including their justification, design,...
Categories: Statistical Theory & Methods, Clinical Trials - Pharmaceutical Science, Statistics & Probability