Sample Size Calculations in Clinical Research. N-Solution Bundle Version + Cd

Summary

This book explains how the formulas and procedures for sample size calculations can be used in a variety of clinical research and development stages. It presents real-world examples from several therapeutic areas and explores emerging topics in pharmaceutical research and development. This edition now provides sample size calculations for dose response studies, microarray studies, and Bayesian approaches. It also includes a basic version of PharmaSoftware Solutions, Inc.’s N Solution 2007. Along with sensitivity analyses for each procedure, the software contains all procedures for testing equality, superiority/noninferiority, and equivalence for comparing means, proportions, and time-to-event data.

Features

• Explains how the formulas and procedures for sample size calculations can be used in a variety of clinical research and development stages
• Presents real-world examples from several therapeutic areas, including cardiovascular medicine, the central nervous system, anti-infective medicine, oncology, and women’s health, to illustrate clinical and statistical concepts, interpretations, and interactions
• Compares the relative merits and disadvantages of statistical methods for sample size calculations
• Provides sample size calculations for three major areas of clinical research: dose response studies, microarray studies, and Bayesian approaches
• Explores emerging topics in pharmaceutical research and development, including QT/QTc studies with time-dependent replicates and the use of propensity score analysis in nonrandomized or observational studies
• Includes a basic version of N Solution 2007, which is the leading software for sample size calculations and power analysis

Table of Contents

Preface
Introduction

• Regulatory Requirement
• Basic Considerations
• Procedures for Sample Size Calculation
• Aims and Structure of the Book

Considerations Prior to Sample Size Calculation

• Confounding and Interaction
• One-Sided Test versus Two-Sided Test
• Crossover Design versus Parallel Design
• Subgroup/Interim Analyses
• Data Transformation
• Practical Issues

Comparing Means

• One-Sample Design
• Two-Sample Parallel Design
• Two-Sample Crossover Design
• Multiple-Sample One-Way ANOVA
• Multiple-Sample Williams Design
• Practical Issues

Large Sample Tests for Proportions

• One-Sample Design
• Two-Sample Parallel Design
• Two-Sample Crossover Design
• One-Way Analysis of Variance
• Williams Design
• Relative Risk—Parallel Design
• Relative Risk—Crossover Design
• Practical Issues

Exact Tests for Proportions

• Binomial Test
• Fisher’s Exact Test
• Optimal Multiple-Stage Designs for Single Arm Trials
• Flexible Designs for Multiple-Arm Trials
• Remarks

Tests for Goodness-of-Fit and Contingency Tables

• Tests for Goodness-of-Fit
• Test for Independence—Single Stratum
• Test for Independence—Multiple Strata
• Test for Categorical Shift
• Carry-Over Effect Test
• Practical Issues

Comparing Time-to-Event Data

• Basic Concepts
• Exponential Model
• Cox’s Proportional Hazards Model
• Weighted Log-Rank Test
• Practical Issues

Group Sequential Methods

• Pocock’s Test
• O’Brien and Fleming’s Test
• Wang and Tsiatis’ Test
• Inner Wedge Test
• Binary Variables
• Time-to-Event Data
• Alpha Spending Function
• Sample Size Re-Estimation
• Conditional Power
• Practical Issues

Comparing Variabilities

• Comparing Intra-Subject Variabilities
• Comparing Intra-Subject CVs
• Comparing Inter-Subject Variabilities
• Comparing Total Variabilities
• Practical Issues

Bioequivalence Testing

• Bioequivalence Criteria
• Average Bioequivalence
• Population Bioequivalence
• Individual Bioequivalence
• In Vitro Bioequivalence

Dose Response Studies

• Continuous Response
• Binary Response
• Time-to-Event Endpoint
• Williams’ Test for Minimum Effective Dose (MED)
• Cochran–Armitage’s Test for Trend
• Dose Escalation Trials
• Concluding Remarks

Microarray Studies

• Literature Review
• False Discovery Rate (FRD) Control
• Family-Wise Error Rate (FWER) Control
• Concluding Remarks

Bayesian Sample Size Calculation

• Posterior Credible Interval Approach
• Posterior Error Approach
• The Bootstrap-Median Approach
• Concluding Remarks

Nonparametrics

• Violation of Assumptions
• One-Sample Location Problem
• Two-Sample Location Problem
• Test for Independence
• Practical Issues

Sample Size Calculation in Other Areas

• QT/QTc Studies with Time-Dependent Replicates
• Propensity Analysis in Nonrandomized Studies
• ANOVA with Repeated Measures
• Quality of Life
• Bridging Studies
• Vaccine Clinical Trials

INDEX