Statistical methods for immunogenicity assessment

259 Pages·2015·4.42 MB·English

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

Statistics S
t
a
t
i
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Immunogenicity assessment is a prerequisite for the successful de- t
i
c
velopment of biopharmaceuticals, including safety and efficacy eval- a
l
uation. Using advanced statistical methods in the study design and M Statistical
analysis stages is therefore essential to immunogenicity risk assess- e
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ment and mitigation strategies. Statistical Methods for Immunoge- h Methods for
o
nicity Assessment provides a single source of information on sta- d
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tistical concepts, principles, methods, and strategies for detection,
f Immunogenicity
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quantification, assessment, and control of immunogenicity.
r

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The book first gives an overview of the impact of immunogenicity on m Assessment
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biopharmaceutical development, regulatory requirements, and sta-
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tistical methods and strategies used for immunogenicity detection, n
o
quantification, and risk assessment and mitigation. It then covers g
e
anti-drug antibody (ADA) assay development, optimization, valida-
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tion, and transfer as well as the analysis of cut point, a key assay ic
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performance parameter in ADA assay development and validation. t
y

The authors illustrate how to apply statistical modeling approach- A
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es to establish associations between ADA and clinical outcomes,
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predict immunogenicity risk, and develop risk mitigation strategies.
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They also present various strategies for immunogenicity risk control.
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The book concludes with an explanation of the computer codes and e
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algorithms of the statistical methods.
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A critical issue in the development of biologics, immunogenicity can
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cause early termination or limited use of the products if not managed a
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well. This book shows how to use robust statistical methods for de- g

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tecting, quantifying, assessing, and mitigating immunogenicity risk.
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It is an invaluable resource for anyone involved in immunogenicity h
a
n
risk assessment and control in both non-clinical and clinical biophar- g

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maceutical development.
Y
u
Harry Yang • Jianchun Zhang
•

Z
h Binbing Yu • Wei Zhao
a
o
K24516
ISBN: 978-1-4987-0034-4
90000
9 781498 700344
www.crcpress.com
K24516_cover.indd 1 6/3/15 10:15 AM
Statistical
Methods for
Immunogenicity
Assessment
Editor-in-Chief
Shein-Chung Chow, Ph.D., Professor, Department of Biostatistics and Bioinformatics,
Duke University School of Medicine, Durham, North Carolina
Series Editors
Byron Jones, Biometrical Fellow, Statistical Methodology, Integrated Information Sciences,
Novartis Pharma AG, Basel, Switzerland
Jen-pei Liu, Professor, Division of Biometry, Department of Agronomy,
National Taiwan University, Taipei, Taiwan
Karl E. Peace, Georgia Cancer Coalition, Distinguished Cancer Scholar, Senior Research Scientist
and Professor of Biostatistics, Jiann-Ping Hsu College of Public Health,
Georgia Southern University, Statesboro, Georgia
Bruce W. Turnbull, Professor, School of Operations Research and Industrial Engineering,
Cornell University, Ithaca, New York
Published Titles
Adaptive Design Methods in Bayesian Methods in Epidemiology
Clinical Trials, Second Edition Lyle D. Broemeling
Shein-Chung Chow and Mark Chang
Bayesian Methods in Health Economics
Adaptive Designs for Sequential Gianluca Baio
Treatment Allocation
Bayesian Missing Data Problems: EM,
Alessandro Baldi Antognini and
Data Augmentation and Noniterative
Alessandra Giovagnoli
Computation
Adaptive Design Theory and Ming T. Tan, Guo-Liang Tian,
Implementation Using SAS and R, and Kai Wang Ng
Second Edition
Bayesian Modeling in Bioinformatics
Mark Chang
Dipak K. Dey, Samiran Ghosh,
Advanced Bayesian Methods for Medical and Bani K. Mallick
Test Accuracy
Benefit-Risk Assessment in
Lyle D. Broemeling
Pharmaceutical Research and
Advances in Clinical Trial Biostatistics Development
Nancy L. Geller Andreas Sashegyi, James Felli, and
Rebecca Noel
Applied Meta-Analysis with R
Ding-Geng (Din) Chen and Karl E. Peace Biosimilars: Design and Analysis of
Follow-on Biologics
Basic Statistics and Pharmaceutical
Shein-Chung Chow
Statistical Applications, Second Edition
James E. De Muth Biostatistics: A Computing Approach
Stewart J. Anderson
Bayesian Adaptive Methods for
Clinical Trials Causal Analysis in Biomedicine and
Scott M. Berry, Bradley P. Carlin, Epidemiology: Based on Minimal
J. Jack Lee, and Peter Muller Sufficient Causation
Mikel Aickin
Bayesian Analysis Made Simple: An Excel
GUI for WinBUGS Clinical and Statistical Considerations
Phil Woodward in Personalized Medicine
Claudio Carini, Sandeep Menon,
Bayesian Methods for Measures of
and Mark Chang
Agreement
Lyle D. Broemeling
Clinical Trial Data Analysis using R DNA Methylation Microarrays:
Ding-Geng (Din) Chen and Karl E. Peace Experimental Design and Statistical
Analysis
Clinical Trial Methodology
Sun-Chong Wang and Arturas Petronis
Karl E. Peace and Ding-Geng (Din) Chen
DNA Microarrays and Related Genomics
Computational Methods in Biomedical
Techniques: Design, Analysis, and
Research
Interpretation of Experiments
Ravindra Khattree and Dayanand N. Naik
David B. Allison, Grier P. Page,
Computational Pharmacokinetics
T. Mark Beasley, and Jode W. Edwards
Anders Källén
Dose Finding by the Continual
Confidence Intervals for Proportions and
Reassessment Method
Related Measures of Effect Size
Ying Kuen Cheung
Robert G. Newcombe
Elementary Bayesian Biostatistics
Controversial Statistical Issues in
Lemuel A. Moyé
Clinical Trials
Empirical Likelihood Method in Survival
Shein-Chung Chow
Analysis
Data Analysis with Competing Risks and
Mai Zhou
Intermediate States
Exposure-Response Modeling: Methods
Ronald B. Geskus
and Practical Implementation
Data and Safety Monitoring Committees
Jixian Wang
in Clinical Trials
Frailty Models in Survival Analysis
Jay Herson
Andreas Wienke
Design and Analysis of Animal Studies in
Generalized Linear Models: A Bayesian
Pharmaceutical Development
Perspective
Shein-Chung Chow and Jen-pei Liu
Dipak K. Dey, Sujit K. Ghosh,
Design and Analysis of Bioavailability and
and Bani K. Mallick
Bioequivalence Studies, Third Edition
Handbook of Regression and Modeling:
Shein-Chung Chow and Jen-pei Liu
Applications for the Clinical and
Design and Analysis of Bridging Studies
Pharmaceutical Industries
Jen-pei Liu, Shein-Chung Chow,
Daryl S. Paulson
and Chin-Fu Hsiao
Inference Principles for Biostatisticians
Design and Analysis of Clinical Trials for
Ian C. Marschner
Predictive Medicine
Interval-Censored Time-to-Event Data:
Shigeyuki Matsui, Marc Buyse,
Methods and Applications
and Richard Simon
Ding-Geng (Din) Chen, Jianguo Sun,
Design and Analysis of Clinical Trials with
and Karl E. Peace
Time-to-Event Endpoints
Introductory Adaptive Trial Designs:
Karl E. Peace
A Practical Guide with R
Design and Analysis of Non-Inferiority
Mark Chang
Trials
Joint Models for Longitudinal and Time-
Mark D. Rothmann, Brian L. Wiens,
to-Event Data: With Applications in R
and Ivan S. F. Chan
Dimitris Rizopoulos
Difference Equations with Public Health
Measures of Interobserver Agreement
Applications
and Reliability, Second Edition
Lemuel A. Moyé and Asha Seth Kapadia
Mohamed M. Shoukri
Medical Biostatistics, Third Edition Sample Size Calculations for Clustered
A. Indrayan and Longitudinal Outcomes in Clinical
Research
Meta-Analysis in Medicine and Health
Chul Ahn, Moonseong Heo, and
Policy
Song Zhang
Dalene Stangl and Donald A. Berry
Sample Size Calculations in Clinical
Mixed Effects Models for the Population
Research, Second Edition
Approach: Models, Tasks, Methods and
Shein-Chung Chow, Jun Shao
Tools
and Hansheng Wang
Marc Lavielle
Statistical Analysis of Human Growth
Modeling to Inform Infectious Disease
and Development
Control
Yin Bun Cheung
Niels G. Becker
Statistical Design and Analysis of
Modern Adaptive Randomized Clinical
Stability Studies
Trials: Statistical and Practical Aspects
Shein-Chung Chow
Oleksandr Sverdlov
Statistical Evaluation of Diagnostic
Monte Carlo Simulation for the
Performance: Topics in ROC Analysis
Pharmaceutical Industry: Concepts,
Kelly H. Zou, Aiyi Liu, Andriy Bandos,
Algorithms, and Case Studies
Lucila Ohno-Machado, and Howard Rockette
Mark Chang
Statistical Methods for Clinical Trials
Multiple Testing Problems in
Mark X. Norleans
Pharmaceutical Statistics
Alex Dmitrienko, Ajit C. Tamhane, Statistical Methods for Drug Safety
and Frank Bretz Robert D. Gibbons and Anup K. Amatya
Noninferiority Testing in Clinical Trials: Statistical Methods for Immunogenicity
Issues and Challenges Assessment
Tie-Hua Ng Harry Yang, Jianchun Zhang, Binbing Yu,
and Wei Zhao
Optimal Design for Nonlinear Response
Models Statistical Methods in Drug Combination
Valerii V. Fedorov and Sergei L. Leonov Studies
Wei Zhao and Harry Yang
Patient-Reported Outcomes:
Measurement, Implementation and Statistics in Drug Research:
Interpretation Methodologies and Recent
Joseph C. Cappelleri, Kelly H. Zou, Developments
Andrew G. Bushmakin, Jose Ma. J. Alvir, Shein-Chung Chow and Jun Shao
Demissie Alemayehu, and Tara Symonds
Statistics in the Pharmaceutical Industry,
Quantitative Evaluation of Safety in Drug Third Edition
Development: Design, Analysis and Ralph Buncher and Jia-Yeong Tsay
Reporting
Survival Analysis in Medicine and
Qi Jiang and H. Amy Xia
Genetics
Randomized Clinical Trials of Jialiang Li and Shuangge Ma
Nonpharmacological Treatments
Theory of Drug Development
Isabelle Boutron, Philippe Ravaud, and
Eric B. Holmgren
David Moher
Translational Medicine: Strategies and
Randomized Phase II Cancer Clinical
Statistical Methods
Trials
Dennis Cosmatos and Shein-Chung Chow
Sin-Ho Jung
Statistical
Methods for
Immunogenicity
Assessment
Harry Yang • Jianchun Zhang
Binbing Yu • Wei Zhao
MedImmune, LLC
Gaithersburg, Maryland, USA
CRC Press
Taylor & Francis Group
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Boca Raton, FL 33487-2742
© 2016 by Taylor & Francis Group, LLC
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No claim to original U.S. Government works
Version Date: 20150515
International Standard Book Number-13: 978-1-4987-0035-1 (eBook - PDF)
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Contents
Preface xv
List of Figures xvii
List of Tables xxi
1 Introduction 1
1.1 Background . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
1.2 Immunogenicity . . . . . . . . . . . . . . . . . . . . . . . . . 4
1.3 Impact of Immunogenicity . . . . . . . . . . . . . . . . . . . 5
1.4 Regulatory Environment and Guidelines . . . . . . . . . . . 6
1.4.1 FDA Guidelines . . . . . . . . . . . . . . . . . . . . . 7
1.4.1.1 Tiered Approach to ADA Assay Development 7
1.4.1.2 Immunogenicity Risk Assessment . . . . . . 9
1.4.2 European Medicines Agency (EMA) Guidance . . . . 13
1.4.2.1 EMA Guidelines on Immunogenicity
Assessment . . . . . . . . . . . . . . . . . . 13
1.4.2.2 Latest Development of EMA Immunogenicity
Guidelines . . . . . . . . . . . . . . . . . . . 14
1.4.3 Japanese Regulatory Requirements of Immunogenicity 14
1.5 Statistics in Immunogenicity Risk Assessment . . . . . . . . 15
1.5.1 In Silico Prediction of Immunogenicity . . . . . . . . . 16
1.5.2 ADA Detection and Quantification . . . . . . . . . . . 16
1.5.3 Clinical Characterization of ADA . . . . . . . . . . . . 17
1.5.3.1 Characteristics of ADA Immune Response . 17
1.5.3.2 Correlation between ADA and PK/PD,
Clinical Safety and Efficacy . . . . . . . . . . 18
1.5.3.3 Relationship of ADA with Clinical Efficacy
and Safety . . . . . . . . . . . . . . . . . . . 18
1.5.3.4 Identification of Risk Factors . . . . . . . . . 18
1.5.4 Control of Immunogenicity Risk . . . . . . . . . . . . 19
1.5.4.1 Control of Process/Product Factors . . . . . 19
1.5.4.2 Biomarkers for Immunogenicity . . . . . . . 19
1.6 Statistical Considerations in Comparative Immunogenicity
Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
ix