Clinical Trial Methodology (Hardcover)

Overview of Clinical Trial Methodology Clinical Trials Clinical Trial MethodologySummary of Clinical Trial Methodology Overview of the Drug Development Process and Regulation of Clinical Trials IntroductionThe Drug Development ProcessHistory of Drug RegulationPrinciples of Adequate and Controlled InvestigationsContent and Format of the INDContent and Format of the NDAOrganizational Structure of the FDAThe 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 IntroductionHistory and Evolution of Ethical Considerations in Clinical Trials: Key MilestonesIndependent Review BoardsClinical Trial Ethics: Who Should Practice?Informed Consent, Sample Size, and PowerCommon Ethical Principles of Various Codes and Regulations Sample Size Considerations in Clinical Trials Pre-Market Approval IntroductionPhases of Clinical Trials and Objectives The Clinical Development Plan: Pre-Market ApprovalSample Size RequirementsExamplesPhilosophical Issues Sequential, Group Sequential, Stochastic Curtailment, and Adaptive Design Procedures in Clinical Trials IntroductionSequential ProceduresGroup Sequential ProceduresStochastic CurtailmentAdaptively Designed Clinical Trials Biostatistical Aspects of the Protocol The Background or Rationale Objective Plan of StudyStatistical Analysis SectionAdministrationProtocol References Section The Statistical Analysis Plan IntroductionProtocol ObjectiveEfficacy Data Collected and Protocol Schema Primary and Secondary Efficacy EndpointsObjectives, Translated as Statistical HypothesesProtocol Design FeaturesStatistical Analyses Pooling of Data from Multicenter Clinical TrialsIntroductionMulticenter Clinical Trial Experimental Setting Pre-Study Planning Multicenter Clinical Trial Conduct Biostatistical Analysis Validity of Statistical InferenceIntroductionPlanning the InvestigationConducting the Investigation Statistical Analyses, Interpretation, and Inference Reporting Results of Investigations Bioequivalence Clinical Trials IntroductionAbsorption, Distribution, Metabolism, and Excretion (ADME) Bioavailability Factors That Affect BioavailabilityBlood Level Clinical Trials BioequivalenceDesign of Bioequivalence TrialsAnalysis of Bioequivalence Trials Analysis of RatiosPharmacokinetic Models Support of Bioequivalence Trials in the Pharmaceutical Industry Examples Dose and Frequency Determination from Phase II Clinical Trials in Stress Test-Induced Angina IntroductionOverview of Response Surface MethodologyFull Quadratic Response Surface ModelPhase 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 IntroductionBackground Objective Designing and Planning the InvestigationConducting the Investigation Statistical AnalysesOther ConsiderationsInnovative Aspects of the Clinical Trial Program Pivotal Proof-of-Efficacy Clinical Trials in the Prevention of NANSAID-Induced Gastric Ulceration IntroductionRationale The ProtocolsMonitoring and Data ManagementFDA Meeting Clinical Trials in the Treatment of Alzheimer’s Disease Based upon Enrichment DesignsIntroductionEnrichment Design Clinical Trials Objective Primary Efficacy Endpoints Sample Size DeterminationStatistical MethodsResults A Clinical Trial to Establish Reduction of CHD Risk IntroductionObjective Designing and Planning the Investigation Conducting the Investigation Data Management Statistical AnalysesResultsSummary Pivotal Proof-of-Efficacy Clinical Trials in the Treatment of Panic Disorder IntroductionDesign of Pivotal Proof-of-Efficacy TrialsTraditional Statistical Analysis Methods Overview of Efficacy Results of the Two Trials Alternative Design and Analysis Strategies Combination Clinical Trials IntroductionTwo-by-Two Factorial Design Effectiveness of the CombinationContribution of Components to the Effectiveness of the Combination Factorial Designs in Other Clinical Development AreasExample 1: Actifed in the Treatment of SAR Following DESI ReviewExample 2: Crossover Trial of Actifed in the Treatment of SARExample 3: Parallel Trial of Actifed in the Treatment of the Common Cold Monitoring Clinical Trials for Adverse Events IntroductionDesigning for Safety: Antibiotic Rash ExampleDesigning for Safety: Hypokalemia Example Designing for Safety: Hypertensive Rebound Example Premarket Approval Trials: Designed for Efficacy Premarket Approval Trials: Quality of Adverse Event InformationMonitoring for SafetyStatistical Methodology: Individual TrialExampleStatistical Methodology: Across Trials Index References appear at the end of each chapter.