title: Assessing incremental value of biomarkers with multi-phase nested case-control studies.
abstract: Accurate risk prediction models are needed to identify different risk groups for individualized prevention and treatment strategies. In the Nurses' Health Study, to examine the effects of several biomarkers and genetic markers on the risk of rheumatoid arthritis (RA), a three-phase nested case-control (NCC) design was conducted, in which two sequential NCC subcohorts were formed with one nested within the other, and one set of new markers measured on each of the subcohorts. One objective of the study is to evaluate clinical values of novel biomarkers in improving upon existing risk models because of potential cost associated with assaying biomarkers. In this paper, we develop robust statistical procedures for constructing risk prediction models for RA and estimating the incremental value (IncV) of new markers based on three-phase NCC studies. Our method also takes into account possible time-varying effects of biomarkers in risk modeling, which allows us to more robustly assess the biomarker utility and address the question of whether a marker is better suited for short-term or long-term risk prediction. The proposed procedures are shown to perform well in finite samples via simulation studies.
authors.affiliation: Department of Statistics and Actuarial Science, Simon Fraser University, Burnaby, BC, Canada, V5A1S6.
authors.forename: Qian M
authors.initials: QM
authors.lastname: Zhou
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Yingye
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Lori B
authors.initials: LB
authors.lastname: Chibnik
authors.affiliation: Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Elizabeth W
authors.initials: EW
authors.lastname: Karlson
authors.affiliation: Department of Biostatistics, Harvard University, Boston, MA, USA.
authors.forename: Tianxi
authors.initials: T
authors.lastname: Cai
mesh_terms: D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000209:etiology; D015415:Biomarkers / Q000032:analysis*; D001699:Biometry / Q000379:methods; D016022:Case-Control Studies; D003198:Computer Simulation; D016208:Databases, Factual / Q000706:statistics & numerical data; D006801:Humans; D015233:Models, Statistical; D015999:Multivariate Analysis; D012307:Risk Factors
chemical_list: D015415:Biomarkers
keywords: Incremental value; Inverse probability weighting; Nested case-control study; Rheumatoid arthritis; Risk prediction; Time dependent ROC curve analysis