TY  - JOUR
AU  - Berger, Moritz
AU  - Klein, Nadja
AU  - Wagner, Michael
AU  - Schmid, Matthias
TI  - Modeling the ratio of correlated biomarkers using copula regression.
JO  - Statistical methods in medical research
VL  - 34
IS  - 5
SN  - 0962-2802
CY  - London [u.a.]
PB  - Sage
M1  - DZNE-2025-00731
SP  - 968 - 985
PY  - 2025
AB  - Modeling the ratio of two dependent components as a function of covariates is a frequently pursued objective in observational research. Despite the high relevance of this topic in medical studies, where biomarker ratios are often used as surrogate endpoints for specific diseases, existing models are commonly based on oversimplified assumptions, assuming e.g. independence or strictly positive associations between the components. In this paper, we overcome such limitations and propose a regression model where the marginal distributions of the two components are linked by a copula. A key feature of our model is that it allows for both positive and negative associations between the components, with one of the model parameters being directly interpretable in terms of Kendall's rank correlation coefficient. We study our method theoretically, evaluate finite sample properties in a simulation study and demonstrate its efficacy in an application to diagnosis of Alzheimer's disease via ratios of amyloid-beta and total tau protein biomarkers.
KW  - Biomarkers
KW  - Humans
KW  - Alzheimer Disease: diagnosis
KW  - Amyloid beta-Peptides
KW  - tau Proteins
KW  - Models, Statistical
KW  - Regression Analysis
KW  - Computer Simulation
KW  - Copula model (Other)
KW  - distributional regression (Other)
KW  - gamma distribution (Other)
KW  - negative dependence (Other)
KW  - ratio outcome (Other)
KW  - Biomarkers (NLM Chemicals)
KW  - Amyloid beta-Peptides (NLM Chemicals)
KW  - tau Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:39930915
C2  - pmc:PMC12177203
DO  - DOI:10.1177/09622802241313293
UR  - https://pub.dzne.de/record/279354
ER  -