Statistical Methods for Immunogenicity Assessment  book cover
1st Edition

Statistical Methods for Immunogenicity Assessment

ISBN 9781498700344
Published September 3, 2015 by Chapman and Hall/CRC
259 Pages 52 B/W Illustrations

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Book Description

Develop Effective Immunogenicity Risk Mitigation Strategies

Immunogenicity assessment is a prerequisite for the successful development of biopharmaceuticals, including safety and efficacy evaluation. Using advanced statistical methods in the study design and analysis stages is therefore essential to immunogenicity risk assessment and mitigation strategies. Statistical Methods for Immunogenicity Assessment provides a single source of information on statistical concepts, principles, methods, and strategies for detection, quantification, assessment, and control of immunogenicity.

The book first gives an overview of the impact of immunogenicity on biopharmaceutical development, regulatory requirements, and statistical methods and strategies used for immunogenicity detection, quantification, and risk assessment and mitigation. It then covers anti-drug antibody (ADA) assay development, optimization, validation, and transfer as well as the analysis of cut point, a key assay performance parameter in ADA assay development and validation. The authors illustrate how to apply statistical modeling approaches to establish associations between ADA and clinical outcomes, predict immunogenicity risk, and develop risk mitigation strategies. They also present various strategies for immunogenicity risk control. The book concludes with an explanation of the computer codes and algorithms of the statistical methods.

A critical issue in the development of biologics, immunogenicity can cause early termination or limited use of the products if not managed well. This book shows how to use robust statistical methods for detecting, quantifying, assessing, and mitigating immunogenicity risk. It is an invaluable resource for anyone involved in immunogenicity risk assessment and control in both non-clinical and clinical biopharmaceutical development.

Table of Contents

Impact of Immunogenicity
Regulatory Environment and Guidelines
Statistics in Immunogenicity Risk Assessment
Statistical Considerations in Comparative Immunogenicity Studies
Concluding Remarks

ADA Assay Development and Validation
ADA Assays
Assay Development and Validation
Design of Experiment
Method Transfer

Determination of ADA Assay Cut Point
Cut Point Experimental Design
Statistical Methods for Cut Point Determination

Clinical Immunogenicity Assessment
Monoclonal Antibodies for the Treatment of Rheumatoid Arthritis (RA)
Statistical Analysis of ADA Status
Effects of ADA on Drug Efficacy
Effect of ADA on AEs
Relationship between ADA and Pharmacokinetics
Statistical Analysis ADA Onset and Duration
Statistical Analysis of ADA Titer

Immunogenicity Risk Control
Risk Assessment
Immunogenicity Risk Control
Biomarkers for Immunogenicity
Concluding Remarks

Computational Tools for Immunogenicity Analysis
Read Data into R
ADA Assay and Cut Point
Implementation of Statistical Analysis of Clinical Immunogenicity Assessment
Graphical Tools for Cause and Effect and Design Space Analysis
Immunogenicity Biomarker Discovery
Report Automation



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Harry Yang is a senior director, Jianchun Zhang is a principal statistician, Binbing Yu is an associate director, and Wei Zhao is a senior principal statistician at MedImmune, LLC in Gaithersburg, Maryland, USA.


"In summary, this book is a good resource to the professionals and practitioners developing the biological therapies, including statisticians, clinicians, pharmacokineticists, regulatory reviewers, toxicologists, clinical assay developers, and biopharmaceutical engineers."
~Journal of Biopharmaceutical Statistics

"The authors' work brings light into some of the issues surrounding immunogenicity of drugs. It is of great help to both clinical and nonclinical professionals, while some of the concepts can also be applied to situations when an immune response towards a drug (a vaccine) is desirable."
~Paul Tudor Tamas