title: Meta-analysis of prognostic studies for a biomarker with a study-specific cutoff value.
abstract: In prognostic studies, a summary statistic such as a hazard ratio is often reported between low-expression and high-expression groups of a biomarker with a study-specific cutoff value. Recently, several meta-analyses of prognostic studies have been reported, but these studies simply combined hazard ratios provided by the individual studies, overlooking the fact that the cutoff values are study-specific. We propose a method to summarize hazard ratios with study-specific cutoff values by estimating the hazard ratio for a 1-unit change of the biomarker in the underlying individual-level model. To this end, we introduce a model for a relationship between a reported log-hazard ratio for a 1-unit expected difference in the mean biomarker value between the low-expression and high-expression groups, which approximates the individual-level model, and propose to make an inference of the model by using the method for trend estimation based on grouped exposure data. Our combined estimator provides a valid interpretation if the biomarker distribution is correctly specified. We applied our proposed method to a dataset that examined the association between the biomarker Ki-67 and disease-free survival in breast cancer patients. We conducted simulation studies to examine the performance of our method. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Kurume University Graduate School of Medicine, 67 Asahi-Machi, Kurume CityFukuoka, 830-0011, Japan.|Shin-Koga Hospital, Medical Corporation Tenjinkai, 120 Tenjin-Chyou, Kurume City, Fukuoka, 830-8577, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Sadashima
authors.affiliation: Biostatistics Center, Kurume University, 67 Asahi-Machi, Kurume City, Fukuoka, 830-0011, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hattori
authors.affiliation: Department of Biostatistics, Nagoya University Graduate School of Medicine, 65, Tsurumai-cho Showa-ku, Nagoya, Aichi, 466-8550, Japan.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Takahashi
mesh_terms: D000465:Algorithms; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality; D003198:Computer Simulation; D003625:Data Collection; D003627:Data Interpretation, Statistical; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D015201:Meta-Analysis as Topic; D011379:Prognosis; D016016:Proportional Hazards Models; D015203:Reproducibility of Results
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen
keywords: biomarker; cutoff value; finite-mixture model; meta-analysis; prognostic study