Bioequivalence Studies in Drug Development (eBook)

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

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 in
single- and multiple-dose bioequivalence studies.

2.1 Introduction.

2.2 Pharmacokinetic characteristics (metrics) for single-dose
studies.

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 additive
model.

References.

4 Assessment of average bioequivalence in the RT/TR
design.

4.1 Introduction.

4.2 The RT/TR crossover design assuming a multiplicative
model.

4.3 Test procedures for bioequivalence assessment.

4.4 Conclusions.

References.

5 Power and sample size determination for testing average
bioequivalence 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 effect
boundaries.

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 clinical
endpoints.

10.1 Introduction.

10.2 Design and testing procedure.

10.3 Power and sample size calculation.

10.4 Conclusions.

Apendix.

References.

Index.

"The book provides an excellent introduction for researchers
approaching the concept of bioequivalence and is a complete and
useful compendium for experienced statisticians." (Biometrical
Journal, April 2009)

"The book provides an important reference providing many worked
examples with real data from drug development. Professionals from
the harmaceutical industry and regulatory bodies will particularly
appreciate the emphasis made on regulatory guidelines."
(Statistical Methods in Medical Research, February 2009)

"Bioequivalence Studies in Drug Development: Methods and
Applications is an informative, timely, and easy-to-read
contribution to bioequivalence and drug-drug/food-drug interaction
literature." (Journal of the American Statistical
Association, September 2008)

"...those statisticians working in this area of research
will find that this book will serve as an excellent reference for
their work..." (Journal of Biopharmaceutical Statistics,
January 2008)

"This book would be beneficial to both pharmaceutical
scientists/researchers and biostatisticians..."
(Biometrics, September 2007)

"For anyone interested in any aspect of bioequivalence, the book
is a very valuable reference." (International Statistical
Review, 2007)

"...my pleasure to review...I would like to add this
book to my book collection of pharmaceutical research and
development." (Biometrics, September 2007)