title: Enhancing efficiency and quality of statistical estimation of immunogenicity assay cut points through standardization and automation.
abstract: Biotherapeutics can elicit immune responses, which can alter the exposure, safety, and efficacy of the therapeutics. A well-designed and robust bioanalytical method is critical for the detection and characterization of relevant anti-drug antibody (ADA) and the success of an immunogenicity study. As a fundamental criterion in immunogenicity testing, assay cut points need to be statistically established with a risk-based approach to reduce subjectivity. This manuscript describes the development of a validated, web-based, multi-tier customized assay statistical tool (CAST) for assessing cut points of ADA assays. The tool provides an intuitive web interface that allows users to import experimental data generated from a standardized experimental design, select the assay factors, run the standardized analysis algorithms, and generate tables, figures, and listings (TFL). It allows bioanalytical scientists to perform complex statistical analysis at a click of the button to produce reliable assay parameters in support of immunogenicity studies.
authors.affiliation: Global Biostatistical Science, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA. Electronic address: csu@amgen.com.
authors.forename: Cheng
authors.initials: C
authors.lastname: Su
authors.affiliation: Global Biostatistical Science, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA. Electronic address: zhoul@amgen.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Pharmacokinetics & Drug Metabolism, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA. Electronic address: zhengh@amgen.com.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Global Biostatistical Science, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA. Electronic address: nweng.email@gmail.com.
authors.forename: Winnie
authors.initials: W
authors.lastname: Weng
authors.affiliation: Information Systems, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA. Electronic address: jayanthi@amgen.com.
authors.forename: Jayanthi
authors.initials: J
authors.lastname: Subramani
authors.affiliation: Pharmacokinetics & Drug Metabolism, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA. Electronic address: vtadkod@amgen.com.
authors.forename: Vineet
authors.initials: V
authors.lastname: Tadkod
authors.affiliation: Clinical Immunology Medical Sciences, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA.. Electronic address: kortneyh1101@gmail.com.
authors.forename: Kortney
authors.initials: K
authors.lastname: Hamilton
authors.affiliation: Pharmacokinetics & Drug Metabolism, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA. Electronic address: amic@amgen.com.
authors.forename: Ami
authors.initials: A
authors.lastname: Bautista
authors.affiliation: Global Biostatistical Science, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA. Electronic address: yuw@amgen.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Clinical Immunology Medical Sciences, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA.. Electronic address: chirmule@gmail.com.
authors.forename: Narendra
authors.initials: N
authors.lastname: Chirmule
authors.affiliation: Pharmacokinetics & Drug Metabolism, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA. Electronic address: zhongz@amgen.com.
authors.forename: Zhandong Don
authors.initials: ZD
authors.lastname: Zhong
mesh_terms: D000465:Algorithms; D000906:Antibodies / Q000276:immunology*; D000917:Antibody Formation / Q000276:immunology*; D001331:Automation / Q000379:methods* / Q000592:standards*; D007118:Immunoassay / Q000379:methods* / Q000592:standards*; D015233:Models, Statistical; D012015:Reference Standards; D012984:Software
chemical_list: D000906:Antibodies
keywords: anti-drug antibody; automated statistical analysis; cut point; equivalence; experimental design; prediction limit