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Overview of Clinical Trial Methodology | |
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Clinical Trials | |
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Clinical Trial Methodology | |
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Summary of Clinical Trial Methodology | |
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Overview of the Drug Development Process and Regulation of Clinical Trials | |
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Introduction | |
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The Drug Development Process | |
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History of Drug Regulation | |
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Principles of Adequate and Controlled Investigations | |
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Content and Format of the IND | |
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Content and Format of the NDA | |
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Organizational Structure of the FDA | |
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The FDA Review Process | |
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Labeling and the Package Insert | |
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Pharmaceutical Company Organization and Role of the Biostatistician | |
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Ethical Considerations in the Design and Conduct of Clinical Trials | |
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Introduction | |
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History and Evolution of Ethical Considerations in Clinical Trials: Key Milestones | |
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Independent Review Boards | |
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Clinical Trial Ethics: Who Should Practice? | |
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Informed Consent, Sample Size, and Power | |
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Common Ethical Principles of Various Codes and Regulations | |
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Sample Size Considerations in Clinical Trials Pre-Market Approval | |
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Introduction | |
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Phases of Clinical Trials and Objectives | |
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The Clinical Development Plan: Pre-Market Approval | |
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Sample Size Requirements | |
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Examples | |
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Philosophical Issues | |
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Sequential, Group Sequential, Stochastic Curtailment, and Adaptive Design Procedures in Clinical Trials | |
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Introduction | |
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Sequential Procedures | |
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Group Sequential Procedures | |
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Stochastic Curtailment | |
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Adaptively Designed Clinical Trials | |
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Biostatistical Aspects of the Protocol | |
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The Background or Rationale | |
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Objective | |
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Plan of Study | |
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Statistical Analysis Section | |
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Administration | |
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Protocol References Section | |
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The Statistical Analysis Plan | |
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Introduction | |
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Protocol Objective | |
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Efficacy Data Collected and Protocol Schema | |
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Primary and Secondary Efficacy Endpoints | |
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Objectives, Translated as Statistical Hypotheses | |
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Protocol Design Features | |
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Statistical Analyses | |
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Pooling of Data from Multicenter Clinical Trials | |
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Introduction | |
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Multicenter Clinical Trial Experimental Setting | |
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Pre-Study Planning | |
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Multicenter Clinical Trial Conduct | |
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Biostatistical Analysis | |
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Validity of Statistical Inference | |
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Introduction | |
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Planning the Investigation | |
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Conducting the Investigation | |
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Statistical Analyses, Interpretation, and Inference | |
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Reporting Results of Investigations | |
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Bioequivalence Clinical Trials | |
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Introduction | |
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Absorption, Distribution, Metabolism, and Excretion (ADME) | |
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Bioavailability | |
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Factors That Affect Bioavailability | |
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Blood Level Clinical Trials | |
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Bioequivalence | |
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Design of Bioequivalence Trials | |
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Analysis of Bioequivalence Trials | |
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Analysis of Ratios | |
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Pharmacokinetic Models | |
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Support of Bioequivalence Trials in the Pharmaceutical Industry | |
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Examples | |
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Dose and Frequency Determination from Phase II Clinical Trials in Stress Test-Induced Angina | |
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Introduction | |
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Overview of Response Surface Methodology | |
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Full Quadratic Response Surface Model | |
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Phase II Clinical Trial Program in Stress Test-Induced Angina | |
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Confirmation of Clinically Optimal Dosing in the Treatment of Duodenal Ulcers: A Phase III Dose Comparison Trial | |
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Introduction | |
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Background | |
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Objective | |
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Designing and Planning the Investigation | |
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Conducting the Investigation | |
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Statistical Analyses | |
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Other Considerations | |
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Innovative Aspects of the Clinical Trial Program | |
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Pivotal Proof-of-Efficacy Clinical Trials in the Prevention of NANSAID-Induced Gastric Ulceration | |
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Introduction | |
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Rationale | |
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The Protocols | |
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Monitoring and Data Management | |
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FDA Meeting | |
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Clinical Trials in the Treatment of Alzheimer's Disease Based upon Enrichment Designs | |
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Introduction | |
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Enrichment Design Clinical Trials | |
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Objective | |
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Primary Efficacy Endpoints | |
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Sample Size Determination | |
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Statistical Methods | |
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Results | |
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A Clinical Trial to Establish Reduction of CHD Risk | |
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Introduction | |
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Objective | |
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Designing and Planning the Investigation | |
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Conducting the Investigation | |
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Data Management | |
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Statistical Analyses | |
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Results | |
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Summary | |
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Pivotal Proof-of-Efficacy Clinical Trials in the Treatment of Panic Disorder | |
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Introduction | |
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Design of Pivotal Proof-of-Efficacy Trials | |
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Traditional Statistical Analysis Methods | |
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Overview of Efficacy Results of the Two Trials | |
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Alternative Design and Analysis Strategies | |
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Combination Clinical Trials | |
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Introduction | |
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Two-by-Two Factorial Design | |
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Effectiveness of the Combination | |
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Contribution of Components to the Effectiveness of the Combination | |
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Factorial Designs in Other Clinical Development Areas | |
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Example 1: Actifed in the Treatment of SAR Following DESI Review | |
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Example 2: Crossover Trial of Actifed in the Treatment of SAR | |
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Example 3: Parallel Trial of Actifed in the Treatment of the Common Cold | |
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Monitoring Clinical Trials for Adverse Events | |
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Introduction | |
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Designing for Safety: Antibiotic Rash Example | |
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Designing for Safety: Hypokalemia Example | |
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Designing for Safety: Hypertensive Rebound Example | |
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Premarket Approval Trials: Designed for Efficacy | |
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Premarket Approval Trials: Quality of Adverse Event Information | |
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Monitoring for Safety | |
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Statistical Methodology: Individual Trial | |
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Example | |
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Statistical Methodology: Across Trials | |
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Index | |
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References appear at the end of each chapter | |