Book description
A complete guide to the key statistical concepts essential for the design and construction of clinical trials
As the newest major resource in the field of medical research, Methods and Applications of Statistics in Clinical Trials, Volume 1: Concepts, Principles, Trials, and Designs presents a timely and authoritative reviewof the central statistical concepts used to build clinical trials that obtain the best results. The referenceunveils modern approaches vital to understanding, creating, and evaluating data obtained throughoutthe various stages of clinical trial design and analysis.
Accessible and comprehensive, the first volume in a two-part set includes newly-written articles as well as established literature from the Wiley Encyclopedia of Clinical Trials. Illustrating a variety of statistical concepts and principles such as longitudinal data, missing data, covariates, biased-coin randomization, repeated measurements, and simple randomization, the book also provides in-depth coverage of the various trial designs found within phase I-IV trials. Methods and Applications of Statistics in Clinical Trials, Volume 1: Concepts, Principles, Trials, and Designs also features:
Detailed chapters on the type of trial designs, such as adaptive, crossover, group-randomized, multicenter, non-inferiority, non-randomized, open-labeled, preference, prevention, and superiority trials
Over 100 contributions from leading academics, researchers, and practitioners
An exploration of ongoing, cutting-edge clinical trials on early cancer and heart disease, mother-to-child human immunodeficiency virus transmission trials, and the AIDS Clinical Trials Group
Methods and Applications of Statistics in Clinical Trials, Volume 1: Concepts, Principles, Trials, and Designs is an excellent reference for researchers, practitioners, and students in the fields of clinicaltrials, pharmaceutics, biostatistics, medical research design, biology, biomedicine, epidemiology,and public health.
Table of contents
- Cover
- Half Title page
- Title page
- Copyright page
- Contributors
- Preface
- Chapter 1: Absolute Risk Reduction
-
Chapter 2: Accelerated Approval
- 2.1 Introduction
- 2.2 Accelerated Development Versus Expanded Access in the U.S.A.
- 2.3 Sorting the Terminology—Which FDA Initiatives Do What?
- 2.4 Accelerated Approval Regulations: 21 C.F.R. 314.500, 314.520, 601.40
- 2.5 Stages of Drug Development and FDA Initiatives
- 2.6 Accelerated Approval Regulations: 21 CFR 314.500, 314.520, 601.40
- 2.7 Accelerated Approval with Surrogate Endpoints
- 2.8 Accelerated Approval with Restricted Distribution
- 2.9 Phase IV Studies/Post Marketing Surveillance
- 2.10 Benefit Analysis for Accelerated Approvals Versus Other Illnesses
- 2.11 Problems, Solutions, and Economic Incentives
- 2.12 Future Directions
- References
- Further Reading
- Chapter 3: AIDS Clinical Trials Group (ACTG)
- Chapter 4: Algorithm-Based Designs
- Chapter 5: Alpha-Spending Function
- Chapter 6: Application of New Designs in Phase I Trials
- Chapter 7: ASCOT Trial
- Chapter 8: Benefit/Risk Assessment in Prevention Trials
-
Chapter 9: Biased Coin Randomization
- 9.1 Randomization Strategies for Overall Treatment Balance
- 9.2 The Biased Coin Randomization Procedure
- 9.3 Properties
- 9.4 Extensions to the Biased Coin Randomization
- 9.5 Adaptive Biased Coin Randomization
- 9.6 Urn Models
- 9.7 Treatment Balance for Covariates
- 9.8 Application of Biased Coin Designs to Response-Adaptive Randomization
- References
-
Chapter 10: Biological Assay, Overview
- 10.1 Introduction
- 10.2 Direct Dilution Assays
- 10.3 Indirect Dilution Assays
- 10.4 Indirect Quantal Assays
- 10.5 Stochastic Approximation in Bioassay
- 10.6 Radioimmunoassay
- 10.7 Dosimetry and Bioassay
- 10.8 Semiparametrics in Bioassays
- 10.9 Nonparametrics in Bioassays
- 10.10 Bioavailability and Bioequivalence Models
- 10.11 Pharmacogenomics in Modern Bioassays
- 10.12 Complexities in Bioassay Modeling and Analysis
- References
- Further Reading
-
Chapter 11: Block Randomization
- 11.1 Introduction
- 11.2 Simple Randomization
- 11.3 Restricted Randomization Through the Use of Blocks
- 11.4 Schemes Using a Single Block for the Whole Trial
- 11.5 Use of Unequal and Variable Block Sizes
- 11.6 Inference and Analysis Following Blocked Randomization
- 11.7 Miscellaneous Topics Related to Blocked Randomization
- References
- Further Reading
- Chapter 12: Censored Data
- Chapter 13: Clinical Data Coordination
- Chapter 14: Clinical Data Management
- Chapter 15: Clinical Significance
-
Chapter 16: Clinical Trial Misconduct
- 16.1 The Scope of this Article
- 16.2 Why Does Research Misconduct Matter?
- 16.3 Early Cases
- 16.4 Definition
- 16.5 Intent
- 16.6 What Scientific Misconduct was Not
- 16.7 The Process
- 16.8 The Past Decade
- 16.9 Lessons from the U.S. Experience
- 16.10 Outside the United States
- 16.11 Scientific Misconduct During Clinical Trials
- 16.12 Audit
- 16.13 Causes
- 16.14 Prevalence
- 16.15 Peer Review and Misconduct
- 16.16 Retractions
- 16.17 Prevention
- References
- Chapter 17: Clinical Trials, Early Cancer and Heart Disease
-
Chapter 18: Cluster Randomization
- 18.1 Introduction
- 18.2 Examples of Cluster Randomization Trials
- 18.3 Principles of Experimental Design
- 18.4 Experimental and Quasi-Experimental Designs
- 18.5 The Effect of Failing to Replicate
- 18.6 Sample Size Estimation
- 18.7 Cluster Level Analyses
- 18.8 Individual Level Analyses
- 18.9 Incorporating Repeated Assessments
- 18.10 Study Reporting
- 18.11 Meta-Analysis
- References
- Chapter 19: Coherence in Phase I Clinical Trials
- Chapter 20: Compliance and Survival Analysis
- Chapter 21: Composite Endpoints in Clinical Trials
- Chapter 22: Confounding
- Chapter 23: Control Groups
- Chapter 24: Coronary Drug Project
- Chapter 25: Covariates
- Chapter 26: Crossover Design
- Chapter 27: Crossover Trials
- Chapter 28: Diagnostic Studies
- Chapter 29: DNA Bank
- Chapter 30: Up-and-Down and Escalation Designs
- Chapter 31: Dose Ranging Crossover Designs
-
Chapter 32: Flexible Designs
- 32.1 Introduction
- 32.2 The General Framework
- 32.3 Conditional Power and Sample Size Reassessment
- 32.4 Extending the Flexibility to the Choice of the Number of Stages
- 32.5 Selection of the Test Statistics
- 32.6 More General Adaptations and Multiple Hypotheses Testing
- 32.7 An Example
- 32.8 Conclusion
- References
- Chapter 33: Gene Therapy
- Chapter 34: Global Assessment Variables
-
Chapter 35: Good Clinical Practice (GCP)
- 35.1 Introduction
- 35.2 Human Rights and Protections
- 35.3 Informed Consent
- 35.4 Investigational Protocol
- 35.5 Investigator’s Brochure
- 35.6 Investigational New Drug Application
- 35.7 Production of the Investigational Drug
- 35.8 Clinical Testing
- 35.9 Sponsors
- 35.10 Contract Research Organization
- 35.11 Monitors
- 35.12 Investigators
- 35.13 Documentation
- 35.14 Clinical Holds
- 35.15 Inspections/Audits
- References
- Further Reading
-
Chapter 36: Group-Randomized Trials
- 36.1 Introduction
- 36.2 Group-Randomized Trials in Context
- 36.3 The Development of Group- Randomized Trials in Public Health
- 36.4 The Range of GRTs in Public Health
- 36.5 Current Design and Analytic Practices in GRTs in Public Health
- 36.6 The Future of Group-Randomized Trials
- 36.7 Planning a New Group-Randomized Trial
- References
- Chapter 37: Group Sequential Designs
-
Chapter 38: Hazard Ratio
- 38.1 Introduction
- 38.2 Definitions
- 38.3 Illustration of Hazard Rate, Hazard Ratio and Risk Ratio
- 38.4 Example on the Use and Usefulness of Hazard Ratios
- 38.5 Ad-hoc Estimator of the Hazard Ratio
- 38.6 Confidence Interval of the Ad-hoc Estimator
- 38.7 Ad-hoc Estimator Stratified for the Covariate Renal Function
- 38.8 Properties of the Ad-hoc Estimator
- 38.9 Class of Generalized Rank Estimators of the Hazard Ratio
- 38.10 Estimation of the Hazard Ratio with Cox’s Proportional Hazards Model
- 38.11 Discussion
- Further Reading
- References
- Chapter 39: Large Simple Trials
- Chapter 40: Longitudinal Data
- Chapter 41: Maximum Duration and Information Trials
- Chapter 42: Missing Data
- Chapter 43: Mother to Child Human Immunodeficiency Virus Transmission Trials
- Chapter 44: Multiple Testing in Clinical Trials
- Chapter 45: Multicenter Trials
- Chapter 46: Multiple Endpoints
- Chapter 47: Multiple Risk Factor Intervention Trial
- Chapter 48: N-of-1 Randomized Trials
-
Chapter 49: Noninferiority Trial
- 49.1 Introduction
- 49.2 Essential Elements of Noninferiority Trial Design
- 49.3 Objectives of Noninferiority Trials
- 49.4 Measure of Treatment Effect
- 49.5 Noninferiority Margin
- 49.6 Statistical Testing for Noninferiority
- 49.7 Medication Nonadherence and Misclassification/Measurement Error
- 49.8 Testing Superiority and Noninferiority
- 49.9 Conclusion
- References
- Chapter 50: Nonrandomized Trials
- Chapter 51: Open-Labeled Trials
- Chapter 52: Optimizing Schedule of Administration in Phase I Clinical Trials
- Chapter 53: Partially Balanced Designs
- Chapter 54: Phase I/II Clinical Trials
- Chapter 55: Phase II/III Trials
- Chapter 56: Phase I Trials
- Chapter 57: Phase II Trials
- Chapter 58: Phase III Trials
- Chapter 59: Phase IV Trials
-
Chapter 60: Phase I Trials in Oncology
- 60.1 Introduction
- 60.2 Dose-Limiting Toxicity
- 60.3 Starting Dose
- 60.4 Dose Level Selection
- 60.5 Study Design and General Considerations
- 60.6 Traditional, Standard, or 3 + 3 Design
- 60.7 Continual Reassessment Method and Other Designs that Target the MTD
- 60.8 Start-Up Rule
- 60.9 Phase I Trials with Long Follow-Up
- 60.10 Phase I Trials with Multiple Agents
- 60.11 Phase I Trials with the MTD Defined using Toxicity Grades
- References
- Further Reading
- Chapter 61: Placebos
-
Chapter 62: Planning a Group-Randomized Trial
- 62.1 Introduction
- 62.2 The Research Question
- 62.3 The Research Team
- 62.4 The Research Design
- 62.5 Potential Design Problems and Methods to Avoid Them
- 62.6 Potential Analytic Problems and Methods to Avoid Them
- 62.7 Variables of Interest and Their Measures
- 62.8 The Intervention
- 62.9 Power
- 62.10 Summary
- References
- Chapter 63: Postmenopausal Estrogen/Progestin Interventions Trial (PEPI)
- Chapter 64: Preference Trials
- Chapter 65: Prevention Trials
-
Chapter 66: Primary Efficacy Endpoint
- 66.1 Defining the Primary Endpoint
- 66.2 Fairness of Endpoints
- 66.3 Specificity of the Primary Endpoint
- 66.4 Composite Primary Endpoints
- 66.5 Missing Primary Endpoint Data
- 66.6 Censored Primary Endpoints
- 66.7 Surrogate Primary Endpoints
- 66.8 Multiple Primary Endpoints
- 66.9 Secondary Endpoints
- References
- Further Reading
- Chapter 67: Prognostic Variables in Clinical Trials
- Chapter 68: Randomization Procedures
- Chapter 69: Randomization Schedule
- Chapter 70: Repeated Measurements
- Chapter 71: Simple Randomization
-
Chapter 72: Subgroups
- 72.1 Introduction
- 72.2 The General Problem
- 72.3 Definitions
- 72.4 Subgroup Effects and Interactions
- 72.5 Tests of Interactions and the Problem of Power
- 72.6 Subgroups and the Problem of Multiple Comparisons
- 72.7 Demographic Subgroups
- 72.8 Physiological Subgroups
- 72.9 Target Subgroups
- 72.10 Improper Subgroups
- 72.11 Summary
- References
-
Chapter 73: Superiority Trials
- 73.1 Introduction
- 73.2 Clinicians Ask One-Sided Questions, and Want Immediate Answers
- 73.3 But Traditional Statistics Is Two-Sided
- 73.4 The Consequences of Two-Sided Answers to One-Sided Questions
- 73.5 The Fallacy of the “Negative” Trial
- 73.6 The Solution Lies in Employing One-Sided Statistics
- 73.7 Examples of Employing One-Sided Statistics
- 73.8 One-Sided Statistical Analyses Need to be Specified Ahead of Time
- 73.9 A Graphic Demonstration of Superiority and Noninferiority
- 73.10 How to Think about and Incorporate Minimally Important Differences
- 73.11 Incorporating Confidence Intervals for Treatment Effects
- 73.12 Why We Should Never Label an “Indeterminate” Trial Result as “Negative” or as Showing “No Effect”
- 73.13 How Does a Treatment Become “Established Effective Therapy”?
- 73.14 Most Trials are Too Small to Declare a Treatment “Established Effective Therapy”
- 73.15 How Do We Achieve a Superiority Result?
- 73.16 Superiority and Noninferiority Trials when Established Effective Therapy Already Exists
- 73.17 Exceptions to the Rule that It Is Always Unethical to Substitute Placebos for Established Effective Therapy
- 73.18 When a Promising New Treatment Might be Added to Established Effective Therapy
- 73.19 Using Placebos in a Trial Should Not Mean the Absence of Treatment
- 73.20 Demonstrating Trials of Promising New Treatments Against (or in Addition to) Established Effective Therapy
- 73.21 Why We Almost Never Find, and Rarely Seek, True “Equivalence”
- 73.22 The Graphical Demonstration of “Superiority” and “Noninferiority”
- 73.23 Completing the Circle: Converting One-Sided Clinical Thinking into One-Sided Statistical Analysis
- 73.24 A Final Note on Superiority and Noninferiority Trials of “Me-Too” Drugs
- References
- Further Reading
- Chapter 74: Surrogate Endpoints
- Chapter 75: TNT Trial
- Chapter 76: UGDP Trial
- Chapter 77: Women’s Health Initiative Hormone Therapy Trials
-
Chapter 78: Women’s Health Initiative Dietary Modification Trial: Update and Application of Biomarker Calibration to Self-Report Measures of Diet and Physical Activity
- 78.1 Rationale for Biomarker Calibration of Self-Report Measures of Diet
- 78.2 Nutrient Biomarker Study Energy and Protein Calibration
- 78.3 Measurement Error Properties of 4DFR, 24HR, and FFQ
- 78.4 Calibration of Self-Report Measures of Physical Activity
- 78.5 Psychosocial Measures and Biomarker-Calibrated Intake
- 78.6 Calibrated Energy, Protein, Protein Density, and Cardiovascular Disease Incidence
- 78.7 Diabetes and Calibrated Consumption
- 78.8 Cancer and Calibrated Intake
- 78.9 Associations Between Protein Intake, Frailty, and Renal Function
- 78.10 Summary and Future Directions
- References
- Index
Product information
- Title: Methods and Applications of Statistics in Clinical Trials, Volume 1: Concepts, Principles, Trials, and Designs
- Author(s):
- Release date: February 2014
- Publisher(s): Wiley
- ISBN: 9781118304730
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