Statistical approaches for the determination of cut points in anti-drug antibody bioassays

Journal of Immunological Methods
Frank SchaarschmidtL A Hothorn

Abstract

Cut points in immunogenicity assays are used to classify future specimens into anti-drug antibody (ADA) positive or negative. To determine a cut point during pre-study validation, drug-naive specimens are often analyzed on multiple microtiter plates taking sources of future variability into account, such as runs, days, analysts, gender, drug-spiked and the biological variability of un-spiked specimens themselves. Five phenomena may complicate the statistical cut point estimation: i) drug-naive specimens may contain already ADA-positives or lead to signals that erroneously appear to be ADA-positive, ii) mean differences between plates may remain after normalization of observations by negative control means, iii) experimental designs may contain several factors in a crossed or hierarchical structure, iv) low sample sizes in such complex designs lead to low power for pre-tests on distribution, outliers and variance structure, and v) the choice between normal and log-normal distribution has a serious impact on the cut point. We discuss statistical approaches to account for these complex data: i) mixture models, which can be used to analyze sets of specimens containing an unknown, possibly larger proportion of ADA-positive specimens...Continue Reading

References

Nov 11, 2008·Journal of Pharmaceutical and Biomedical Analysis·Gopi ShankarEugen Koren
Aug 4, 2009·Biologicals : Journal of the International Association of Biological Standardization·L A HothornM Hofmann
May 13, 2011·Journal of Pharmaceutical and Biomedical Analysis·Thomas JakiFrank Horling
Sep 13, 2011·Journal of Immunological Methods·David Hoffman, Marion Berger
Dec 19, 2012·Journal of Pharmaceutical and Biomedical Analysis·Robert J KubiakLorin K Roskos
Jan 12, 2013·Journal of Immunological Methods·Lanju ZhangHarry Yang
Jul 11, 2013·Journal of Pharmaceutical and Biomedical Analysis·Daniel ColemanEric Wakshull
Sep 10, 2013·Journal of Pharmaceutical and Biomedical Analysis·Thomas JakiFrank Horling
Apr 5, 2014·Journal of Biopharmaceutical Statistics·Jianchun ZhangHarry Yang

❮ Previous
Next ❯

Citations

Jun 6, 2016·Journal of Pharmaceutical and Biomedical Analysis·Thomas JakiFrank Horling
Sep 14, 2016·Journal of Pharmaceutical and Biomedical Analysis·Woo Hyuck ChoiSang Kyum Kim
Jan 9, 2017·Journal of Immunological Methods·Jianchun ZhangHarry Yang
Jun 27, 2019·Journal of Biopharmaceutical Statistics·Qi XiaYu-Ting Weng
Jul 25, 2017·The AAPS Journal·Viswanath DevanarayanRonald R Bowsher
Aug 9, 2021·Regulatory Toxicology and Pharmacology : RTP·Felix M KluxenThomas Hofmann

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.