Randomized Clinical Trials ─ Design, Practice and Reporting

Using examples and case studies from industry, academia and research literature, Randomized Clinical Trials provides a detailed overview of the key issues involved in designing, conducting, analysing and reporting randomized clinical trials.� It examines the methodology for conducting Phase III clinical trials, developing the protocols, the practice for capturing, measuring, and analysing the resulting clinical data and their subsequent reporting.
Randomized clinical trials are the principal method for determining the relative efficacy and safety of alternative treatments, interventions or medical devices.� They are conducted by groups comprising one or more of pharmaceutical and allied health-care organisations, academic institutions, and charity supported research groups.� In many cases such trials provide the key evidence necessary for the regulatory approval of a new product for future patient use.� Randomized Clinical Trials provides comprehensive coverage of such trials, ranging from elementary to advanced level.
Written by authors with considerable experience of clinical trials, Randomized Clinical Trials is an authoritative guide for clinicians, nurses, data managers and medical statisticians involved in clinical trials research and for health care professionals directly involved in patient care in a clinical trial context.

David Machin, Medical Statistics Group, School of Health and Related Sciences, University of Sheffield, UK and Children's Cancer and Leukaemia Group, University of Leicester, UK
Peter M Fayers, Department of Public Health, University of Aberdeen, UK and Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway

"Randomized Clinical Trials: Design, Practice and Reporting is a solid introduction for clinical research investigators." (The Journal of Clinical Research Best Practices, February 2011)
"In summary, this text is ambitious in its scope (possibly to a fault), but certainly fills a void in the literature in the sense that it provides a comprehensive overview of the planning, execution, and reporting of clinical trials that is unparalleled." (Journal of Biopharmaceutical Statistics (JBS), February 2011)
"Randomized Clinical Trials aims to bring bang up to date all the recent major developments in the important field of clinical trial methodology and statistics. A supremely important subject to all of us, this is surely a more worthy new year investment than that month’s supply of dandelion liver flush tonic." (Health Writer, Autumn 2009)

Preface.
1 Introduction.
1.1 Introduction.
1.2 Some completed trials.
1.3 Choice of design.
1.4 Practical constraints.
1.5 Influencing clinical practice.
1.6 History.
1.7 How trials arise.
1.8 Ethical considerations.
1.9 Regulatory requirements.
1.10 Focus.
1.11 Further reading.
2 Design Features.
2.1 Introduction.
2.2 The research question.
2.3 Patient selection.
2.4 The consent process.
2.5 Choice of interventions.
2.6 Choice of design.
2.7 Assigning the interventions.
2.8 Making the assessments.
2.9 Analysis and reporting.
2.10 Technical details.
2.11 Guidelines.
2.12 Further reading.
3 The Trial Protocol.
3.1 Introduction.
3.2 Protocol – abstract.
3.3 Protocol – background.
3.4 Protocol – research objectives.
3.5 Protocol – design.
3.6 Protocol – intervention details.
3.7 Protocol – eligibility.
3.8 Protocol – randomization.
3.9 Protocol – assessment and data collection.
3.10 Protocol – statistical considerations.
3.11 Protocol – ethical issues.
3.12 Protocol – organizational structure.
3.13 Protocol – publication policy.
3.14 Protocol – trial forms.
3.15 Protocol – appendices.
3.16 Regulatory requirements.
3.17 Guidelines.
3.18 Protocols.
4 Measurement and Data Capture.
4.1 Introduction.
4.2 Measures and endpoints.
4.3 Making the observations.
4.4 Baseline measures.
4.5 Types of measures.
4.6 Data recording.
4.7 Technical notes.
4.8 Guidelines.
5 Randomization.
5.1 Introduction.
5.2 Rationale.
5.3 Mechanics.
5.4 Application.
5.5 Carrying out randomization.
5.6 Documentation.
5.7 Unacceptable methods.
5.8 Software.
5.9 Guidelines.
6 Trial Initiation.
6.1 Introduction.
6.2 Trial organization.
6.3 Data collection and processing.
6.4 Data monitoring.
6.5 Ethical and regulatory requirements.
6.6 Launching the trial.
6.7 Trial registries.
6.8 Guidelines.
7 Trial Conduct.
7.1 Introduction.
7.2 Regular feedback.
7.3 Publicity.
7.4 Data monitoring committees.
7.5 Protocol modifications.
7.6 Preparing the publication(s).
7.7 The next trial?
7.8 Protocols.
8 Basics of Analysis.
8.1 Introduction.
8.2 Confidence intervals.
8.3 Statistical tests.
8.4 Examples of analysis.
8.5 Other issues.
8.6 Practice.
8.7 Technical details.
9 Trial Size.
9.1 Introduction.
9.2 Significance level and power.
9.3 The fundamental equation.
9.4 Specific situations.
9.5 Practical considerations.
9.6 Further topics.
9.7 Other methods and software.
9.8 Guideline.
10 Reporting.
10.1 Introduction.
10.2 Publication guidelines.
10.3 Responsibilities.
10.4 Background.
10.5 Methods.
10.6 Findings.
10.7 When things go wrong.
10.8 Conclusions.
10.9 Guidelines.
11 Adaptations of the Basic Design.
11.1 Introduction.
11.2 Repeated measures.
11.3 Cluster-randomized trials.
11.4 Non-inferiority trials.
11.5 Guidelines.
12 Paired Designs.
12.1 Cross-over trials.
12.2 Split-mouth designs.
12.3 Paired organs.
13 More Than Two Interventions.
13.1 Introduction.
13.2 Unstructured comparisons.
13.3 Comparisons with placebo (or standard).
13.4 Dose response designs.
13.5 Factorial trials.
14 Further Topics.
14.1 Introduction.
14.2 Adaptive approaches.
14.3 Large simple trials.
14.4 Bayesian methods.
14.5 Zelen randomized-consent designs.
14.6 Systematic overviews.
14.7 Conclusion.
Statistical Tables.
Glossary.
References.
Index.