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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 | |