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List of figures | |
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List of tables | |
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Preface | |
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Author Attribution | |
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Introduction to Clinical Trials | |
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History and Background | |
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Ethics of Clinical Research | |
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Types of Research Design and Types of Trials | |
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The Need for Clinical Trials | |
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The Randomization Principle | |
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Timing of a Clinical Trial | |
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Trial Organization | |
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Protocol and Manual of Operations | |
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Regulatory Issues | |
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Overview of the Book | |
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Defining the Question | |
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Statistical Framework | |
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Elements of Study Question | |
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Outcome or Response Measures | |
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The Surrogate Outcome | |
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Composite Outcomes | |
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Summary | |
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Problems | |
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Study Design | |
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Early Phase Trials | |
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Phase III/IV Trials | |
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Non-inferiority Designs | |
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Screening, Prevention, and Therapeutic Designs | |
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Adaptive Designs | |
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Conclusions | |
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Problems | |
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Sample Size | |
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Sample Size versus Information | |
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A General Setup for Frequentist Designs | |
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Loss to Follow-up and Non-adherence | |
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Survival Data | |
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Clustered Data | |
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Tests for Interaction | |
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Equivalence/Non-inferiority Trials | |
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Other Considerations | |
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Problems | |
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Randomization | |
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The Role of Randomization | |
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Fixed Randomization Procedures | |
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Treatment- and Response-Adaptive Randomization Procedures | |
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Covariate-Adaptive Randomization Procedures | |
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Summary and Recommendations | |
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Problems | |
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Data Collection and Quality Control | |
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Planning for Collection of Clinical Trial Data | |
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Categories of Clinical Data | |
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Data Quality Control | |
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Conclusions | |
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Survival Analysis | |
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Background | |
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Estimation of Survival Distributions | |
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Comparison of Survival Distributions | |
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Regression Models | |
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Composite Outcomes | |
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Summary | |
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Problems | |
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Longitudinal Data | |
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A Clinical Longitudinal Data Example | |
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The Subject-specific Model | |
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Two-stage Estimation | |
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The Random-effects, Subject-specific Model | |
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The Population-average (Marginal) Model | |
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Restricted Maximum Likelihood Estimation (REML) | |
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Standard Errors | |
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Testing | |
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Additional Levels of Clustering | |
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Generalized Estimating Equations for Non-normal Data | |
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Missing Data | |
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Summary | |
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Quality of Life | |
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Defining QoL | |
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Types of QoL Assessments | |
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Selecting a QoL Instrument | |
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Developing a QoL Instrument | |
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Quality of Life Data | |
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Analysis of QoL Data | |
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Summary | |
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Data Monitoring and Interim Analysis | |
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Data and Safety Monitoring | |
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Examples | |
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The Repeated Testing Problem | |
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Group Sequential Tests | |
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Triangular Test | |
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Curtailment Procedures | |
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Inference Following Sequential Tests | |
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Discussion | |
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Problems | |
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Selected Issues in the Analysis | |
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Bias in the Analysis of Clinical Trial Data | |
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Choice of Analysis Population | |
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Missing Data | |
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Subgroup Analyses | |
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Multiple Testing Procedures | |
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Summary | |
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Problems | |
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Closeout and Reporting | |
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Closing Out a Trial | |
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Reporting Trial Results | |
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Problems | |
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Delta Method, Maximum Likelihood Theory, and Information | |
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Delta Method | |
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Asymptotic Theory for Likelihood Based Inference | |
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Hypothesis Testing | |
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Computing the MLE | |
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Information | |
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Brownian Motion | |
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References | |
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Index | |