Confidence Interval Estimation for Sensitivity to the Early Diseased Stage Based on Empirical Likelihood

Abstract

Many disease processes can be divided into three stages: the non-diseased stage: the early diseased stage, and the fully diseased stage. To assess the accuracy of diagnostic tests for such diseases, various summary indexes have been proposed, such as volume under the surface (VUS), partial volume under the surface (PVUS), and the sensitivity to the early diseased stage given specificity and the sensitivity to the fully diseased stage (P₂). This paper focuses on confidence interval estimation for P₂ based on empirical likelihood. Simulation studies are carried out to assess the performance of the new methods compared to the existing parametric and nonparametric ones. A real dataset from Alzheimer’s Disease Neuroimaging Initiative (ADNI) is analyzed.

Key words:

• Diagnostic tests
• Empirical likelihood
• The sensitivity to the early diseased stage.

ACKNOWLEDGMENTS

Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.ucla.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at http://adni.loni.ucla.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.

Additional information

Funding

Data collection and sharing for this project was funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd. and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. The ADNI research was also supported by NIH grants P30 AG010129 and K01 AG030514.