Clinical Trial Methodology

Clinical Trial Methodology

  • Electronic book text
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Now viewed as its own scientific discipline, clinical trial methodology encompasses the methods required for the protection of participants in a clinical trial and the methods necessary to provide a valid inference about the objective of the trial. Drawing from the authors' courses on the subject as well as the first author's more than 30 years working in the pharmaceutical industry, Clinical Trial Methodology emphasizes the importance of statistical thinking in clinical research and presents the methodology as a key component of clinical research.

From ethical issues and sample size considerations to adaptive design procedures and statistical analysis, the book first covers the methodology that spans every clinical trial regardless of the area of application. Crucial to the generic drug industry, bioequivalence clinical trials are then discussed. The authors describe a parallel bioequivalence clinical trial of six formulations incorporating group sequential procedures that permit sample size re-estimation. The final chapters incorporate real-world case studies of clinical trials from the authors' own experiences. These examples include a landmark Phase III clinical trial involving the treatment of duodenal ulcers and Phase III clinical trials that contributed to the first drug approved for the treatment of Alzheimer's disease.

Aided by the U.S. FDA, the U.S. National Institutes of Health, the pharmaceutical industry, and academia, the area of clinical trial methodology has evolved over the last six decades into a scientific discipline. This guide explores the processes essential for developing and conducting a quality clinical trial protocol and providing quality data collection, biostatistical analyses, and a clinical study report, all while maintaining the highest standards of ethics and excellence.
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Product details

  • Electronic book text | 420 pages
  • Taylor & Francis Ltd
  • Chapman & Hall/CRC
  • London, United Kingdom
  • 263 - PPI 496; 83 Tables, black and white; 34 Illustrations, black and white
  • 1584889187
  • 9781584889182

Table of contents

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
References appear at the end of each chapter.
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Review quote

This comprehensive text introduces the key areas of clinical trial methodology from the perspective of the biostatistician in the pharmaceutical industry. ... Throughout, the text benefits from a highly structured and logical flow ... the arguments made in the book are grounded in many years of practical experience in drug development and at the very least will act as a prompt for in-depth discussion or critical review of one's own perceptions. ... Clinical Trial Methodology will be of substantial value to early career pharmaceutical industry statisticians.-Christopher J. Weir, Pharmaceutical Statistics, 2012
... informative discussions of mechanisms such as IND and NDA ... are unique strengths of this book, distinguishing it from the many other clinical trial texts available. ... Case studies ... are presented carefully ... The authors' writing style is disciplined, careful, and informative. ... this is a helpful and informative book, a nice reference to have for most biostatisticians working on clinical trials.-Mithat Gonen, Journal of Biopharmaceutical Statistics, 21, 2011
The book is an excellent overview predicated on the first author's seasoned experiences in designing, analyzing, and communicating the results of clinical trials across a broad number of medical disciplines. ... A nice introductory feature is the history of drug law and regulation, which helps to frame the subsequent statistical discussion nicely. ... The real-world examples that dominate the last few chapters are fantastic. ... There is nothing like a series of examples from an experienced clinical trialist to whet the appetite of those involved in the noble enterprise of medical (and more specifically pharmaceutical) research with the goal of improving the public's health. This book does an admirable job in giving the regulatory and statistical foundations for clinical trials, coupled with real-world examples of how statistical methodology has guided the development of important medicines. ...-Gregory Enas
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About Karl E. Peace

Karl E. Peace is the Georgia Cancer Coalition Distinguished Cancer Scholar, founding director of the Center for Biostatistics, and professor of biostatistics in the Jiann-Ping Hsu College of Public Health at Georgia Southern University.
Din Chen is the Karl E. Peace Endowed Eminent Scholar Chair in Biostatistics and professor of biostatistics in the Jiann-Ping Hsu College of Public Health at Georgia Southern University.
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