Sample Sizes for Clinical Trials

Abstract

Introduction Background to Randomized Controlled Trials Types of Clinical Trial Assessing Evidence from Trials Superiority Trials Equivalence Trials Non-Inferiority Trials As-Good-as-or-Better Trials Assessment of Bioequivalence Estimation to a Given Precision Seven Key Steps to Cook up a Sample Size Introduction Step 1: Deciding on the Trial Objective Step 2: Deciding on the Endpoint Step 3: Determining the Effect Size (or Margin) Step 4: Assessing the Population Variability Step 5: Type I Error Step 6: Type II Error Step 7: Other Factors Sample Sizes for Parallel Group Superiority Trials with Normal Data Introduction Sample Sizes Estimated Assuming the Population Variance to Be Known Design Considerations Revisiting Worked Example Sensitivity Analysis Calculations Taking Account of the Imprecision of the Variance Used in the Sample Size Calculations Interim Analyses and Sample Size Re-Estimation Cluster Randomized Trials Sample Size Calculations for Superiority Crossover Trials with Normal Data Introduction Sample Sizes Estimated Assuming the Population Variance to Be Known Sensitivity Analysis about the Variance Used in the Sample Size Calculations Calculations Taking Account of the Imprecision of the Variance Used in the Sample Size Calculations Sample Size Calculations for Equivalence Clinical Trials with Normal Data Introduction Parallel Group Trials Crossover Trials Sample Size Calculations for Non-Inferiority Clinical Trials with Normal Data Introduction Parallel Group Trials Crossover Trials As-Good-as-or-Better Trials Sample Size Calculations for Bioequivalence Trials Introduction Crossover Trials Parallel Group Studies Sample Size Calculations for Precision-Based Clinical Trials with Normal Data Introduction Parallel Group Trials Crossover Trials Sample Size Calculations for Parallel Group Superiority Clinical Trials with Binary Data Introduction Inference and Analysis of Clinical Trials with Binary Data Sample Sizes with the Population Effects Assumed Known Inclusion of Baselines or Covariates Sample Size Re-Estimation Sensitivity Analysis about the Estimates of the Population Effects Used in the Sample Size Calculations Calculations Taking Account of the Imprecision of the Estimates of the Population Effects Used in the Sample Size Calculations Calculations Taking Account of the Imprecision of the Estimates Used in the Sample Size Calculations: Bayesian Methods Sample Size Calculations for Superiority Crossover Clinical Trials with Binary Data Introduction Analysis of a Trial Analysis of a Trial Revisited Sensitivity Analysis about the Estimates of the Population Effects Used in the Sample Size Calculations Calculations Taking Account of the Imprecision of the Estimates of the Population Effects Used in the Sample Size Calculations Calculations Taking Account of the Imprecision of the Estimates Used in the Sample Size Calculations: Bayesian Methods Sample Size Calculations for Non-Inferiority Trials with Binary Data Introduction Choice of Non-Inferiority Limit Parallel Group Trials Sample Size with the Population Effects Assumed Known As-Good-as-or-Better Trials Sample Size Calculations for Equivalence Trials with Binary Data Introduction Parallel Group Trials Crossover Trials Sample Size Calculations for Precision-Based Trials with Binary Data Introduction Parallel Group Trials Crossover Trials Sample Size Calculations for Clinical Trials with Ordinal Data Introduction The Quality-of-Life Data Superiority Trials Non-Inferiority Trials As-Good-as-or-Better Trials Equivalence Trials Estimation to a Given Precision Sample Size Calculations for Clinical Trials with Survival Data Introduction Superiority Trials Non-Inferiority Trials Equivalence Trials Precision-Based Trials References Appendix