Rights statement: This is the author’s version of a work that was accepted for publication in Journal of Pharmaceutical and Biomedical Analysis. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Pharmaceutical and Biomedical Analysis, 128, 2016 DOI: 10.1016/j.jpba.2016.05.031
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Final published version
Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - A false sense of security?
T2 - can tiered approach be trusted to accurately classify immunogenicity samples?
AU - Jaki, Thomas Friedrich
AU - Allacher, Peter
AU - Horling, Frank
N1 - This is the author’s version of a work that was accepted for publication in Journal of Pharmaceutical and Biomedical Analysis. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Pharmaceutical and Biomedical Analysis, 128, 2016 DOI: 10.1016/j.jpba.2016.05.031
PY - 2016/9/5
Y1 - 2016/9/5
N2 - Detecting and characterizing of anti-drug antibodies (ADA) against a protein therapeutic are crucially important to monitor the unwanted immune response. Usually a multi-tiered approach that initially rapidly screens for positive samples that are subsequently confirmed in a separate assay is employed for testing of patient samples for ADA activity. In this manuscript we evaluate the ability of different methods used to classify subject with screening and competition based confirmatory assays. We find that for the overall performance of the multi-stage process the method used for confirmation is most important where a t-test is best when differences are moderate to large. Moreover we find that, when differences between positive and negative samples are not sufficiently large, using a competition based confirmation step does yield poor classification of positive samples.
AB - Detecting and characterizing of anti-drug antibodies (ADA) against a protein therapeutic are crucially important to monitor the unwanted immune response. Usually a multi-tiered approach that initially rapidly screens for positive samples that are subsequently confirmed in a separate assay is employed for testing of patient samples for ADA activity. In this manuscript we evaluate the ability of different methods used to classify subject with screening and competition based confirmatory assays. We find that for the overall performance of the multi-stage process the method used for confirmation is most important where a t-test is best when differences are moderate to large. Moreover we find that, when differences between positive and negative samples are not sufficiently large, using a competition based confirmation step does yield poor classification of positive samples.
KW - Anti-drug antibody
KW - Confirmatory
KW - cut point
KW - immunoassay
KW - immunogenicity
KW - screening
KW - specificity
U2 - 10.1016/j.jpba.2016.05.031
DO - 10.1016/j.jpba.2016.05.031
M3 - Journal article
VL - 128
SP - 166
EP - 173
JO - Journal of Pharmaceutical and Biomedical Analysis
JF - Journal of Pharmaceutical and Biomedical Analysis
SN - 0731-7085
ER -