A false sense of security? Can tiered approach be trusted to accurately classify immunogenicity samples?
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.
Medical and Pharmaceutical Statistics Research Unit, Department of Mathematics and Statistics, Lancaster University, Lancaster, United Kingdom. Electronic address: jaki.thomas@gmail.com.
Thomas
T
Jaki
Baxalta Innovations GmbH, Industriestrasse 67, 1221 Vienna, Austria; IMC University of Applied Sciences, Piaristengasse 1, 3500 Krems an der Donau, Austria.
Peter
P
Allacher
Baxalta Innovations GmbH, Industriestrasse 67, 1221 Vienna, Austria.
Frank
F
Horling
D000465:Algorithms; D000906:Antibodies / Q000032:analysis*; D000911:Antibodies, Monoclonal / Q000276:immunology; D003198:Computer Simulation; D005188:False Negative Reactions; D005189:False Positive Reactions; D006801:Humans; D007120:Immunochemistry / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000032:analysis*
D000906:Antibodies; D000911:Antibodies, Monoclonal; D004364:Pharmaceutical Preparations
Anti-drug antibody; Confirmatory; Cut point; Immunoassay; Immunogenicity; Screening; Specificity