Statistical Issues in Drug Development

Statistical Issues in Drug Development
 
The revised third edition of Statistical Issues in Drug Development delivers an insightful treatment of the intersection between statistics and the life sciences. The book offers readers new discussions of crucial topics, including cluster randomization, historical controls, responder analysis, studies in children, post-hoc tests, estimands, publication bias, the replication crisis, and many more.
 
This work presents the major statistical issues in drug development in a way that is accessible and comprehensible to life scientists working in the field, and takes pains not to gloss over significant disagreements in the field of statistics, while encouraging communication between the statistical and life sciences disciplines. In addition to new material on topics like invalid inversion, severity, random effects in network meta-analysis, and explained variation, readers will benefit from the inclusion of:
* A thorough introduction to basic topics in drug development and statistics, including the role played by statistics in drug development
* An exploration of the four views of statistics in drug development, including the historical, methodological, technical, and professional
* An examination of debatable and controversial topics in drug development, including the allocation of treatments to patients in clinical trials, baselines and covariate information, and the measurement of treatment effects
 
Perfect for life scientists and other professionals working in the field of drug development, Statistical Issues in Drug Development is the ideal resource for anyone seeking a one-stop reference to enhance their understanding of the use of statistics during drug development.

List of contents

Preface to the Third Edition
 
Preface to the Second Edition xiii
 
Preface to the First Edition xvii
 
Acknowledgements xxi
 
1 Introduction 1
 
1.1 Drug development 1
 
1.2 The role of statistics in drug development 2
 
1.3 The object of this book 3
 
1.4 The author's knowledge of statistics in drug development 4
 
1.5 The reader and his or her knowledge of statistics 4
 
1.6 How to use the book 5
 
References 6
 
Part 1 Four Views of Statistics in Drug Development: Historical, Methodological, Technical and Professional 9
 
2 A Brief and Superficial History of Statistics for Drug Developers 11
 
2.1 Introduction 11
 
2.2 Early Probabilists 12
 
2.3 James Bernoulli (1654-1705) 13
 
2.4 John Arbuthnott (1667-1753) 14
 
2.5 The mathematics of probability in the late 17th, the 18th and early 19th centuries 14
 
2.6 Thomas Bayes (1701-1761) 15
 
2.7 Adolphe Quetelet (1796-1874) 16
 
2.8 George Biddell Airy (1801-1892)
 
2.9 Francis Galton (1822-1911) 16
 
2.10 Karl Pearson (1857-1936) 17
 
2.11 'Student' (1876-1937) 17
 
2.12 R.A. Fisher (1890-1962) 17
 
2.13 Modern mathematical statistics 18
 
2.14 Medical statistics 19
 
2.15 Statistics in clinical trials today 20
 
2.16 The current debate 21
 
2.17 A living science 21
 
2.18 Further reading 23
 
References 23
 
3 Design and Interpretation of Clinical Trials as Seen by a Statistician 27
 
3.1 Prefatory warning 27
 
3.2 Introduction 27
 
3.3 Defining effects 28
 
3.4 Practical problems in using the counterfactual argument 28
 
3.5 Regression to the mean 29
 
3.6 Control in clinical trials 33
 
3.7 Randomization 34
 
3.8 Blinding 36
 
3.9 Using concomitant observations 37
 
3.10 Measuring treatment effects 38
 
3.11 Data generation models 39
 
3.12 In conclusion 41
 
3.13 Further reading 41
 
References 41
 
4 Probability, Bayes, P-values, Tests of Hypotheses and Confidence Intervals 43
 
4.1 Introduction 43
 
4.2 An example 44
 
4.3 Odds and sods 44
 
4.4 The Bayesian solution to the example 45
 
4.5 Why don't we regularly use the Bayesian approach in clinical trials? 46
 
4.6 A frequentist approach 47
 
4.7 Hypothesis testing in controlled clinical trials 48
 
4.8 Significance tests and P-values 49
 
4.9 Confidence intervals and limits and credible intervals 50
 
4.10 Some Bayesian criticism of the frequentist approach 51
 
4.11 Decision theory 51
 
4.12 Conclusion 52
 
4.13 Further reading 52
 
References 53
 
5 The Work of the Pharmaceutical Statistician 55
 
5.1 Prefatory remarks 55
 
5.2 Introduction 56
 
5.3 In the beginning 57
 
5.4 The trial protocol 57
 
5.5 The statistician's role in planning the protocol 58
 
5.6 Sample size determination 59
 
5.7 Other important design issues 60
 
5.8 Randomization 60
 
5.9 Data collection preview 61
 
5.10 Performing the trial 61
 
5.11 Data analysis preview 61
 
5.12 Analysis and reporting 62
 
5.13 Other activities 63
 
5.14 Statistical research 63
 
5.15 Further reading 64
 
References 65
 
Part 2 Statistical Issues: Debatable and Controversial Topics in Drug Development 67
 
6 Allocating Treatments to Patients in Clinical Trials 69
 
6.1 Backgr

About the author

Professor Stephen Senn (MSc, PhD, CStat) is a statistical consultant, researcher and blogger. He has extensive experience in both academia and industry, and is recognized worldwide for his studies in statistical methodology applied to drug development.
Professor Senn has been the recipient of national and international awards, including the 1st George C Challis award for Biostatistics at the University of Florida, and the Bradford Hill Medal of the Royal Statistical Society. He is a Fellow of the Royal Society of Edinburgh and an honorary life member of Statisticians in the Pharmaceutical Industry (PSI) and the International Society for Clinical Biostatistics (ISCB) and has honorary professorships in statistics at The University of Sheffield and the University of Edinburgh.

Summary

Statistical Issues in Drug Development

The revised third edition of Statistical Issues in Drug Development delivers an insightful treatment of the intersection between statistics and the life sciences. The book offers readers new discussions of crucial topics, including cluster randomization, historical controls, responder analysis, studies in children, post-hoc tests, estimands, publication bias, the replication crisis, and many more.

This work presents the major statistical issues in drug development in a way that is accessible and comprehensible to life scientists working in the field, and takes pains not to gloss over significant disagreements in the field of statistics, while encouraging communication between the statistical and life sciences disciplines. In addition to new material on topics like invalid inversion, severity, random effects in network meta-analysis, and explained variation, readers will benefit from the inclusion of:
* A thorough introduction to basic topics in drug development and statistics, including the role played by statistics in drug development
* An exploration of the four views of statistics in drug development, including the historical, methodological, technical, and professional
* An examination of debatable and controversial topics in drug development, including the allocation of treatments to patients in clinical trials, baselines and covariate information, and the measurement of treatment effects

Perfect for life scientists and other professionals working in the field of drug development, Statistical Issues in Drug Development is the ideal resource for anyone seeking a one-stop reference to enhance their understanding of the use of statistics during drug development.

Product details

• Authors: S Senn, Stephen S Senn, Stephen S. Senn, Stephen S. (University College Senn, Senn Stephen S.
• Publisher: Wiley, John and Sons Ltd
• Languages: English
• Product format: Hardback
• Released: 18.03.2021
• EAN: 9781119238577
• ISBN: 978-1-119-23857-7
• No. of pages: 640
• Series: Statistics in Practice
• Subjects: Natural sciences, medicine, IT, technology > Mathematics > Probability theory, stochastic theory, mathematical statistics; Statistik, Arzneimittel, Medizin, Medizinische Statistik, Statistics, Produktentwicklung, Biostatistik, Biostatistics, Pharmacology & Pharmaceutical Medicine, Pharmakologie u. Pharmazeutische Medizin, Medical Science, Angewandte Wahrscheinlichkeitsrechnung u. Statistik, Applied Probability & Statistics