» Articles » PMID: 38445348

Combining Multiple Biomarkers Linearly to Minimize the Euclidean Distance of the Closest Point on the Receiver Operating Characteristic Surface to the Perfection Corner in Trichotomous Settings

Overview
Publisher Sage Publications
Specialties Public Health
Science
Date 2024 Mar 6
PMID 38445348
Authors
Affiliations
Soon will be listed here.
Abstract

The performance of individual biomarkers in discriminating between two groups, typically the healthy and the diseased, may be limited. Thus, there is interest in developing statistical methodologies for biomarker combinations with the aim of improving upon the individual discriminatory performance. There is extensive literature referring to biomarker combinations under the two-class setting. However, the corresponding literature under a three-class setting is limited. In our study, we provide parametric and nonparametric methods that allow investigators to optimally combine biomarkers that seek to discriminate between three classes by minimizing the Euclidean distance from the receiver operating characteristic surface to the perfection corner. Using this Euclidean distance as the objective function allows for estimation of the optimal combination coefficients along with the optimal cutoff values for the combined score. An advantage of the proposed methods is that they can accommodate biomarker data from all three groups simultaneously, as opposed to a pairwise analysis such as the one implied by the three-class Youden index. We illustrate that the derived true classification rates exhibit narrower confidence intervals than those derived from the Youden-based approach under a parametric, flexible parametric, and nonparametric kernel-based framework. We evaluate our approaches through extensive simulations and apply them to real data sets that refer to liver cancer patients.

References
1.
Bantis L, Tsimikas J, Georgiou S . Smooth ROC curves and surfaces for markers subject to a limit of detection using monotone natural cubic splines. Biom J. 2013; 55(5):719-40. DOI: 10.1002/bimj.201200158. View

2.
Bantis L, Nakas C, Reiser B . Construction of confidence intervals for the maximum of the Youden index and the corresponding cutoff point of a continuous biomarker. Biom J. 2018; 61(1):138-156. DOI: 10.1002/bimj.201700107. View

3.
Youden W . Index for rating diagnostic tests. Cancer. 1950; 3(1):32-5. DOI: 10.1002/1097-0142(1950)3:1<32::aid-cncr2820030106>3.0.co;2-3. View

4.
Perkins N, Schisterman E . The inconsistency of "optimal" cutpoints obtained using two criteria based on the receiver operating characteristic curve. Am J Epidemiol. 2006; 163(7):670-5. PMC: 1444894. DOI: 10.1093/aje/kwj063. View

5.
Dolin H, Papadimos T, Stepkowski S, Chen X, Pan Z . A Novel Combination of Biomarkers to Herald the Onset of Sepsis Prior to the Manifestation of Symptoms. Shock. 2017; 49(4):364-370. PMC: 5811232. DOI: 10.1097/SHK.0000000000001010. View