Statistical Methods for Immunogenicity Assessment: 1st Edition (Hardback) book cover

Statistical Methods for Immunogenicity Assessment

1st Edition

By Harry Yang, Jianchun Zhang, Binbing Yu, Wei Zhao

Chapman and Hall/CRC

259 pages | 52 B/W Illus.

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Hardback: 9781498700344
pub: 2015-09-03
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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.


"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

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



About the Authors

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.

About the Series

Chapman & Hall/CRC Biostatistics Series

Learn more…

Subject Categories

BISAC Subject Codes/Headings:
MATHEMATICS / Probability & Statistics / General
MEDICAL / Pharmacy
MEDICAL / Biostatistics