2nd Edition

Bioequivalence and Statistics in Clinical Pharmacology

By Scott D. Patterson, Byron Jones Copyright 2017
    460 Pages
    by Chapman & Hall

    460 Pages 75 B/W Illustrations
    by Chapman & Hall

    460 Pages 75 B/W Illustrations
    by Chapman & Hall

    Maintaining a practical perspective, Bioequivalence and Statistics in Clinical Pharmacology, Second Edition explores statistics used in day-to-day clinical pharmacology work. The book is a starting point for those involved in such research and covers the methods needed to design, analyze, and interpret bioequivalence trials; explores when, how, and why these studies are performed as part of drug development; and demonstrates the methods using real world examples.





    Drawing on knowledge gained directly from working in the pharmaceutical industry, the authors set the stage by describing the general role of statistics. Once the foundation of clinical pharmacology drug development, regulatory applications, and the design and analysis of bioequivalence trials are established, including recent regulatory changes in design and analysis and in particular sample-size adaptation, they move on to related topics in clinical pharmacology involving the use of cross-over designs. These include, but are not limited to, safety studies in Phase I, dose-response trials, drug interaction trials, food-effect and combination trials, QTc and other pharmacodynamic equivalence trials, proof-of-concept trials, dose-proportionality trials, and vaccines trials. 





    This second edition addresses several recent developments in the field, including new chapters on adaptive bioequivalence studies, scaled average bioequivalence testing, and vaccine trials.





    Purposefully designed to be instantly applicable, Bioequivalence and Statistics in Clinical Pharmacology, Second Edition provides examples of SAS and R code so that the analyses described can be immediately implemented. The authors have made extensive use of the proc mixed procedures available in SAS.

    Bioequivalence & Biopharmaceutical Development



    Drug Development and Clinical Pharmacology



    Aims of This Book



    Biopharmaceutical Development



    Clinical Pharmacology



    Statistics in Clinical Pharmacology



    Structure of the Book



    History and Regulation of Bioequivalence



    When and How BE Studies Are Performed



    Why Are BE Studies Performed?



    Deciding When Formulations Are Bioequivalent



    Potential Issues with TOST Bioequivalent



    Current International Regulation



    Some Practical Notes



    Testing for Average Bioequivalence



    Background



    Linear Model for 2 x 2 Data



    Applying the TOST Procedure



    Carry-over, Sequence, and Interaction Effects



    Checking Assumptions Made about the Linear Model



    Power and Sample Size for ABE in the 2 x 2 Design



    Example Where Test and Reference Are Not ABE



    Nonparametric Analysis



    BE Studies with More Than Two Periods



    Background



    Three-period Designs



    Within-subject Variability



    Robust Analyses for Three Period Designs



    Four-period Designs



    Designes with More Than Two Treatments



    Adjusting for Multiple Testing



    Nonparametric Analyses of Tmax



    Technical appendix: Efficiency



    Tables of Data



    Special Topics in Bioequivalence



    Dealing with Special BE Challenges



    Restricted Maximum Likelihood Modelling



    Failing BE and the DER Assessment



    Simulation



    Data-based Simulation



    Carry-over



    Optimal Designs



    Determining Trial Size



    What Outliers Are and How to Handle Their Data



    Bayesian BE Assessment



    Adaptive Bioequivalence Trials



    Background



    Two-stage design for testing for ABE



    TOST using the standard combination test



    Example of using the standard combination test



    The maximum combination test



    Example of using the maximum combination test



    Conditional errors and conditional power



    Algorithm for sample size re-estimation



    Operating characteristics



    Conclusions



    Techniccal Appendix: R code



    Scaled Average Bioequivalence Testing



    Background



    Scaled Average Bioequivalence in Europe



    Scaled Average Bioequivalence in USA



    Discussion and Cautions



    Clinical Pharmacology



    Clinical Pharmacology Safety Studies



    Background



    First-time-in-humans



    Sub-chronic Dosing Studies



    Food-Effect Assessment and DDIs



    Dose-Proportionality



    Technical Appendix



    QTc



    Background



    Modelling of QTc Data



    Interpreting the QTc Modelling Findings



    Design of a Thorough QTc Study in the Future



    Clinical Pharmacology Efficacy Studies



    Background



    Sub-chronic Dosing



    Phase IIa and the Proof of Concept



    Population Pharmacokinetics



    Population and Pharmacokinetics



    Absolute and Relative Bioavailabili

    Biography

    Scott D. Patterson, Byron Jones