Clinical Trial Methodology

ISBN: 9780367577155 出版年：2010 页码：422 Peace, Karl E Chen, Ding-Geng (Din) CRC Press

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