Hauschke / Steinijans / Pigeot Bioequivalence Studies in Drug Development

Methods and Applications
1. Auflage 2007
ISBN: 978-0-470-09476-1
Verlag: John Wiley & Sons
Format: PDF
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, 328 Seiten, E-Book

Reihe: Statistics in Practice

Studies in bioequivalence are the commonly accepted method todemonstrate therapeutic equivalence between two medicinal products.Savings in time and cost are substantial when using bioequivalenceas an established surrogate marker of therapeutic equivalence. Forthis reason the design, performance and evaluation ofbioequivalence studies have received major attention from academia,the pharmaceutical industry and health authorities.
Bioequivalence Studies in Drug Development focuses on theplanning, conducting, analysing and reporting of bioequivalencestudies, covering all aspects required by regulatory authorities.This text presents the required statistical methods, and with anoutstanding practical emphasis, demonstrates their applicationsthrough numerous examples using real data from drugdevelopment.
* Includes all the necessary pharmacokinetic backgroundinformation.
* Presents parametric and nonparametric statisticaltechniques.
* Describes adequate methods for power and sample sizedetermination.
* Includes appropriate presentation of results frombioequivalence studies.
* Provides a practical overview of the design and analysis ofbioequivalence studies.
* Presents the recent developments in methodology, includingpopulation and individual bioequivalence.
* Reviews the regulatory guidelines for such studies, and theexisting global discrepancies.
* Discusses the designs and analyses of drug-drug and food-druginteraction studies.
Bioequivalence Studies in Drug Development is written inan accessible style that makes it ideal for pharmaceuticalscientists, clinical pharmacologists, and medical practitioners, aswell as biometricians working in the pharmaceutical industry. Itwill also be of great value for professionals from regulatorybodies assessing bioequivalence studies.

Autoren/Hrsg.

Hauschke, Dieter

Steinijans, Volker

Pigeot, Iris

Inhaltsverzeichnis

Preface.
1 Introduction.
1.1 Definitions.
1.2 When are bioequivalence studies performed.
1.3 Design and conduct of bioequivalence studies.
1.4 Aims and structure of the book.
References.
2 Metrics to characterize concentration-time profiles insingle- and multiple-dose bioequivalence studies.
2.1 Introduction.
2.2 Pharmacokinetic characteristics (metrics) for single-dosestudies.
2.3 Pharmacokinetic rate and extent characteristics (metrics)for multiple-dose studies.
2.4 Conclusions.
References.
3 Basic statistical considerations.
3.1 Introduction.
3.2 Additive and multiplicative model.
3.3 Hypotheses testing.
3.4 The RT/TR crossover design assuming an additivemodel.
References.
4 Assessment of average bioequivalence in the RT/TRdesign.
4.1 Introduction.
4.2 The RT/TR crossover design assuming a multiplicativemodel.
4.3 Test procedures for bioequivalence assessment.
4.4 Conclusions.
References.
5 Power and sample size determination for testing averagebioequivalence in the RT/TR design.
5.1 Introduction.
5.2 Challenging the classical approach.
5.3 Exact power and sample size calculation.
5.4 Modified acceptance ranges.
5.5 Approximate formulas for sample size calculation.
5.6 Exact power and sample size calculation by nQuery®.
References.
Appendix.
6 Presentation of bioequivalence studies.
6.1 Introduction.
6.2 Results from a single-dose study.
6.3 Results from a multiple-dose study.
6.4 Conclusions.
References.
7 Designs with more than two formulations.
7.1 Introduction.
7.2 Williams designs.
7.3 Example: Dose linearity study.
7.4 Multiplicity.
7.5 Conclusions.
References.
8 Analysis of pharmacokinetic interactions.
8.1 Introduction.
8.2 Pharmacokinetic drug-drug interaction studies.
8.3 Pharmacokinetic food-drug interactions.
8.4 Goal posts for drug interaction studies including no effectboundaries.
8.5 Labeling.
8.6 Conclusions.
References.
9 Population and individual bioequivalence.
9.1 Introduction.
9.2 Brief history.
9.3 Study designs and statistical models.
9.4 Population bioequivalence.
9.5 Individual bioequivalence.
9.6 Disaggregate criteria.
9.7 Other approaches.
9.8 Average bioequivalence in replicate designs.
9.9 Example: The anti-hypertensive patch dataset.
9.10 Conclusions.
References.
10 Equivalence assessment in case of clinicalendpoints.
10.1 Introduction.
10.2 Design and testing procedure.
10.3 Power and sample size calculation.
10.4 Conclusions.
Apendix.
References.
Index.

Über Autor(innen)

Dieter Hauschke, ALTANA Pharma, Konstanz, Germany.Well-respected statistician working in the pharmaceutical industry,specializing in bioequivalence studies, with over 60 publicationsin leading journals.
Volker Steinijans, ALTANA Pharma, Konstanz, Germany. Headof the Department of Biometry and Clinical Data Management atALTANA.
Iris Pigeot, Institute for Statistics, University ofBremen, Germany. Has over 50 published papers, and also written anumber of books in German.