Design and Analysis of Bioavailability and Bioequivalence Studies, Third Edition BABE-Solution bundle version: (Chapman & Hall/CRC Biostatistics Series)

Containing four new chapters, along with several new and updated sections, this third edition reviews the latest progress of activities and results in bioavailability and bioequivalence on regulatory requirements, scientific and practical issues, and statistical methodology. It presents the current status of regulations on bioavailability and bioequivalence, including guidelines/guidances issued by the FDA, EMEA, and WHO. This edition addresses frequently asked questions and explores sample size determination, meta-analysis, and pharmacokinetics. It also offers a basic version of PharmaSoftware Solutions, Inc.’s BABE Solution 2008, with bioequivalence assessment for in vivo bioequivalence studies.

Table of Contents:
Preface Preliminaries Introduction History of Bioavailability Studies Formulation and Routes of Administration Pharmacokinetic Parameters Clinically Important Differences Assessment of Bioequivalence Decision Rules and Regulatory Aspects Statistical Considerations Aims and Structure of the Book Design of Bioavailability Studies Introduction Study Objective Basic Design Considerations Parallel Design The Crossover Design Balanced Incomplete Block Design Selection of Design Statistical Inference for Effects from a Standard 2 × 2 Crossover Design Introduction Carryover Effects Direct Drug Effect Period Effect Analysis of Variance An Example Average Bioequivalence Statistical Methods for Average Bioequivalence Introduction Confidence Interval Approach Methods of Interval Hypothesis Testing Bayesian Methods Nonparametric Methods Discussion and Other Alternatives Power and Sample Size Determination Introduction Hypotheses and Type I and Type II Errors Power and Relative Efficiency Sample Size Determination Transformation and Analysis of Individual Subject Ratios Introduction Multiplicative (or Log-Transformed) Model Bioequivalence Measures Maximum Likelihood Estimator Minimum Variance Unbiased Estimator Mean of Individual Subject Ratios Ratio of Formulation Means Comparison of MLE, MVUE, MIR, and RM An Example Discussion Assessment of Inter- and Intrasubject Variabilities Introduction Variability and Decision Making Point and Interval Estimates Test for Equality of Variabilities Equivalence in Variability of Bioavailability CV Assessment Discussion Assumptions of Outlier Detection for Average Bioequivalence Introduction Tests for Assumptions Definition of Outlying Observations Detection of Outlying Subjects Detection of Outlying Observations Discussion Optimal Crossover Designs for Two Formulations for Average Bioequivalence Introduction Balaam’s Design Two-Sequence Dual Design Optimal Four-Period Designs Transformation and Individual Subject Ratios Sample Size for Higher-Order Crossover Designs Discussion Assessment of Average Bioequivalence for More Than Two Formulations Introduction Assessment of Average Bioavailability with More Than Two Formulations Analyses for Williams Designs Analysis for Balanced Incomplete Block Design Discussion Population and Individual Bioequivalence Population and Individual Bioequivalence Introduction Limitation of Average Bioequivalence Merits of Individual Bioequivalence and Desirable Bioequivalence Criteria Measures of Discrepancy Probability-Based Criteria Moment-Based Criteria Relations among Criteria Bioequivalence Limits Designs for Population and Individual Bioequivalence Discussion Statistical Procedures for Assessment of Population and Individual Bioequivalence Introduction Estimation Procedures Procedures for Moment-Based Criteria Procedures for Probability-Based Criteria Generalized p-Values for Evaluation of Population Bioequivalence Discussion In Vitro and Alternative Evaluation of Bioequivalence Assessment of Bioequivalence for Drugs with Negligible Plasma Levels Introduction Design and Clinical Endpoints Statistical Considerations Weighted Least Squares Methods Log-Linear Models Generalized Estimating Equations Analysis of Time to Onset of a Therapeutic Response Discussion In Vitro Bioequivalence Testing Introduction Study Design and Data Collection Bioequivalence Limit Statistical Methods An Example Sample Size Determination Discussion In Vitro Dissolution Profiles Comparison Introduction Criterion for Assessment of Similarity between Dissolution Profiles Inference for Similarity Factors Approaches Based on Multivariate Confidence Regions An Example Discussion Other Bioequivalence Studies Meta-Analysis for Bioequivalence Review Introduction Meta-Analysis for Average Bioequivalence Alternative Method for Meta-Analysis Efficiency of Meta-Analysis Discussion Population Pharmacokinetics Introduction Regulatory Requirements Population PK Modeling Design of Population PK An Example Discussion Other Pharmacokinetic Studies Introduction Drug Interaction Studies Dose Proportionality Study Steady-State Analysis Evaluation of Food Effects Discussion Review of Regulatory Guidances on Bioequivalence Introduction Guidances on Statistical Procedures Guidances on General Considerations for Bioequivalence Guidances on Bioequivalence for Special Drug Products Critical Path Opportunities for Generic Drugs Discussion Frequently Asked Questions and Future Challenges Introduction Assessment of Bioequivalence Using Genomic Information Bridging Bioequivalence Studies Bioequivalence for Biological Products Frequently Asked Questions in Bioequivalence Discussion References Appendix A: Statistical Tables Appendix B: SAS Programs Index

About the Author :
Duke University School of Medicine, Durham, North Carolina, USA National Taiwan University, Taipei