@article{9151184db53646f087e6aab79084d4dd,
title = "Developing biomarker combinations in multicenter studies via direct maximization and penalization",
abstract = "Motivated by a study of acute kidney injury, we consider the setting of biomarker studies involving patients at multiple centers where the goal is to develop a biomarker combination for diagnosis, prognosis, or screening. As biomarker studies become larger, this type of data structure will be encountered more frequently. In the presence of multiple centers, one way to assess the predictive capacity of a given combination is to consider the center-adjusted area under the receiver operating characteristic curve (aAUC), a summary of the ability of the combination to discriminate between cases and controls in each center. Rather than using a general method, such as logistic regression, to construct the biomarker combination, we propose directly maximizing the aAUC. Furthermore, it may be desirable to have a biomarker combination with similar performance across centers. To that end, we allow for penalization of the variability in the center-specific AUCs. We demonstrate desirable asymptotic properties of the resulting combinations. Simulations provide small-sample evidence that maximizing the aAUC can lead to combinations with improved performance. We also use simulated data to illustrate the utility of constructing combinations by maximizing the aAUC while penalizing variability. Finally, we apply these methods to data from the study of acute kidney injury.",
keywords = "adjusted AUC, biomarker combinations, multicenter, penalization",
author = "Allison Meisner and Parikh, {Chirag R.} and Kerr, {Kathleen F.}",
note = "Funding Information: information National Heart, Lung, and Blood Institute, R01 HL085757; National Institute of Diabetes and Digestive and Kidney Diseases, F31 DK108356; K24 DK090203This work was supported by the National Institutes of Health (F31 DK108356, R01 HL085757, and K24 DK090203). The opinions, results, and conclusions reported in this article are those of the authors and are independent of the funding sources. The authors wish to acknowledge the TRIBE-AKI study investigators: Steven G. Coca (Department of Internal Medicine, Icahn School of Medicine at Mount Sinai, New York, New York), Amit X. Garg (Institute for Clinical Evaluative Sciences Western, London, Ontario, Canada; Division of Nephrology, Department of Medicine, and Department of Epidemiology and Biostatistics, University of Western Ontario, London, Ontario, Canada), Jay Koyner (Section of Nephrology, Department of Medicine, University of Chicago Pritzker School of Medicine, Chicago, Illinois), and Michael Shlipak (Kidney Health Research Collaborative, San Francisco Veterans Affairs Medical Center, University of California, San Francisco, San Francisco, California). Urine NGAL, plasma h-FABP, and plasma cardiac troponin I assays used in the TRIBE-AKI study were donated by Abbott Diagnostics, Randox Laboratories, and Beckman Coulter, respectively. Funding Information: This work was supported by the National Institutes of Health (F31 DK108356, R01 HL085757, and K24 DK090203). The opinions, results, and conclusions reported in this article are those of the authors and are independent of the funding sources. The authors wish to acknowledge the TRIBE‐AKI study investigators: Steven G. Coca (Department of Internal Medicine, Icahn School of Medicine at Mount Sinai, New York, New York), Amit X. Garg (Institute for Clinical Evaluative Sciences Western, London, Ontario, Canada; Division of Nephrology, Department of Medicine, and Department of Epidemiology and Biostatistics, University of Western Ontario, London, Ontario, Canada), Jay Koyner (Section of Nephrology, Department of Medicine, University of Chicago Pritzker School of Medicine, Chicago, Illinois), and Michael Shlipak (Kidney Health Research Collaborative, San Francisco Veterans Affairs Medical Center, University of California, San Francisco, San Francisco, California). Urine NGAL, plasma h‐FABP, and plasma cardiac troponin I assays used in the TRIBE‐AKI study were donated by Abbott Diagnostics, Randox Laboratories, and Beckman Coulter, respectively. Publisher Copyright: {\textcopyright} 2020 John Wiley & Sons, Ltd.",
year = "2020",
month = oct,
day = "30",
doi = "10.1002/sim.8673",
language = "English (US)",
volume = "39",
pages = "3412--3426",
journal = "Statistics in Medicine",
issn = "0277-6715",
publisher = "John Wiley and Sons Ltd",
number = "24",
}