Construction of confidence intervals for the maximum of the Youden index and the corresponding cutoff point of a continuous biomarker.

Bantis, Leonidas E; Nakas, Christos T.; Reiser, Benjamin (2019). Construction of confidence intervals for the maximum of the Youden index and the corresponding cutoff point of a continuous biomarker. Biometrical journal, 61(1), pp. 138-156. Wiley-VCH 10.1002/bimj.201700107

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Evaluation of the overall accuracy of biomarkers might be based on average measures of the sensitivity for all possible specificities -and vice versa- or equivalently the area under the receiver operating characteristic (ROC) curve that is typically used in such settings. In practice clinicians are in need of a cutoff point to determine whether intervention is required after establishing the utility of a continuous biomarker. The Youden index can serve both purposes as an overall index of a biomarker's accuracy, that also corresponds to an optimal, in terms of maximizing the Youden index, cutoff point that in turn can be utilized for decision making. In this paper, we provide new methods for constructing confidence intervals for both the Youden index and its corresponding cutoff point. We explore approaches based on the delta approximation under the normality assumption, as well as power transformations to normality and nonparametric kernel- and spline-based approaches. We compare our methods to existing techniques through simulations in terms of coverage and width. We then apply the proposed methods to serum-based markers of a prospective observational study involving diagnosis of late-onset sepsis in neonates.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute of Clinical Chemistry

UniBE Contributor:

Nakas, Christos T.

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0323-3847

Publisher:

Wiley-VCH

Language:

English

Submitter:

Alexandra Müller

Date Deposited:

03 Jan 2020 12:51

Last Modified:

03 Jan 2020 12:51

Publisher DOI:

10.1002/bimj.201700107

PubMed ID:

30408224

Uncontrolled Keywords:

Box-Cox transformation ROC curve Youden index delta method kernels sensitivity specificity splines

BORIS DOI:

10.7892/boris.136903

URI:

https://boris.unibe.ch/id/eprint/136903

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