Statistics Applied to Clinical Trials

1. Front Matter

   Pages i-xiii

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2. Hypotheses, Data, Stratification

   • Ton J. Cleophas, Aeilko H. Zwinderman, Toine F. Cleophas

   Pages 1-16

3. The Analysis of Efficacy Data of Drug Trials

   • Ton J. Cleophas, Aeilko H. Zwinderman, Toine F. Cleophas

   Pages 17-38

4. The Analysis of Safety Data of Drug Trials

   • Ton J. Cleophas, Aeilko H. Zwinderman, Toine F. Cleophas

   Pages 39-46

5. Equivalence Testing

   • Ton J. Cleophas, Aeilko H. Zwinderman, Toine F. Cleophas

   Pages 47-52

6. Statistical Power and Sample Size

   • Ton J. Cleophas, Aeilko H. Zwinderman, Toine F. Cleophas

   Pages 53-64

7. Interim Analyses

   • Ton J. Cleophas, Aeilko H. Zwinderman, Toine F. Cleophas

   Pages 65-71

8. Multiple Statistical Inferences

   • Ton J. Cleophas, Aeilko H. Zwinderman, Toine F. Cleophas

   Pages 73-82

9. Principles of Linear Regression

   • Ton J. Cleophas, Aeilko H. Zwinderman, Toine F. Cleophas

   Pages 83-94

10. Subgroup Analysis using Multiple Linear Regression: Confounding, Interaction, Synergism

    • Ton J. Cleophas, Aeilko H. Zwinderman, Toine F. Cleophas

    Pages 95-104

11. Curvilinear Regression

    • Ton J. Cleophas, Aeilko H. Zwinderman, Toine F. Cleophas

    Pages 105-117

12. Meta-Analysis

    • Ton J. Cleophas, Aeilko H. Zwinderman, Toine F. Cleophas

    Pages 119-132

13. Crossover Studies with Continuous Variables: Power Analysis

    • Ton J. Cleophas, Aeilko H. Zwinderman, Toine F. Cleophas

    Pages 133-142

14. Crossover Studies with Binary Responses

    • Ton J. Cleophas, Aeilko H. Zwinderman, Toine F. Cleophas

    Pages 143-150

15. Post-Hoc Analysis in Clinical Trials, a Case for Logistic Regression Analysis

    • Ton J. Cleophas, Aeilko H. Zwinderman, Toine F. Cleophas

    Pages 151-155

16. Quality-of-Life Assessments in Clinical Trials

    • Ton J. Cleophas, Aeilko H. Zwinderman, Toine F. Cleophas

    Pages 157-166

17. Statistical Analysis of Genetic Data

    • Ton J. Cleophas, Aeilko H. Zwinderman, Toine F. Cleophas

    Pages 167-176

18. Relationship among Statistical Distributions

    • Ton J. Cleophas, Aeilko H. Zwinderman, Toine F. Cleophas

    Pages 177-189

19. Statistics is Not “Bloodless” Algebra

    • Ton J. Cleophas, Aeilko H. Zwinderman, Toine F. Cleophas

    Pages 191-197

20. Back Matter

    Pages 199-210

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In 1948 the first randomized controlled trial was published by the English Medical Research Council in the British Medical Journal. Until then, observations had been uncontrolled. Initially, trials frequently did not confirm hypotheses to be tested. This phenomenon was attributed to low sensitivity due to small samples, as well as inappropriate hypotheses based on biased prior trials. Additional flaws were recognized and subsequently were better accounted for: carryover effects due to insufficient washout from previous treatments, time effects due to external factors and the natural history of the condition under study, bias due to asymmetry between treatment groups, lack of sensitivity due to a negative correlation between treatment responses, etc. Such flaws, mainly of a technical nature, have been largely corrected and led to trials after 1970 being of significantly better quality than before. The past decade has focused, in addition to technical aspects, on the need for circumspection in planning and conducting of clinical trials. As a consequence, prior to approval, clinical trial protocols are now routinely scrutinized by different circumstantial bodies, including ethics committees, institutional and federal review boards, national and international scientific organizations, and monitoring committees charged with conducting interim analyses.
This book not only explains classical statistical analyses of clinical trials, but addresses relatively novel issues, including equivalence testing, interim analyses, sequential analyses, and meta-analyses, and provides a framework of the best statistical methods currently available for such purposes. The book is not only useful for investigators involved in the field of clinical trials, but also for all physicians who wish to better understand the data of trials as currently published.

• Logistic Regression
• Regression analysis
• correlation
• linear regression
• statistical inference
• statistics

• European Interuniversity College of Pharmaceutical Medicine Lyon, France

  Ton J. Cleophas, Aeilko H. Zwinderman

• Department Medicine, Albert Schweitzer Hospital, Dordrecht, The Netherlands

  Ton J. Cleophas

• Department Biostatistics and Epidemiology, Academic Medical Center Amsterdam, The Netherlands

  Aeilko H. Zwinderman

• Technical University, Delft, The Netherlands

  Toine F. Cleophas

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