title: Regression modeling with recurrent events and time-dependent interval-censored marker data.
abstract: In life history studies involving patients with chronic diseases it is often of interest to study the relationship between a marker process and a more clinically relevant response process. This interest may arise from a desire to gain a better understanding of the underlying pathophysiology, a need to evaluate the utility of the marker as a potential surrogate outcome, or a plan to conduct inferences based on joint models. We consider data from a trial of breast cancer patients with bone metastases. In this setting, the marker process is a point process which records the onset times and cumulative number of bone lesions which reflects the extent of metastatic bone involvement The response is also a point process, which records the times patients experience skeletal complications resulting from these bone lesions. Interest lies in assessing how the development of new bone lesions affects the incidence of skeletal complications. By considering the marker as an internal time-dependent covariate in the point process model for skeletal complications we develop and apply methods which allow one to express the association via regression. A complicating feature of this study is that new bone lesions are only detected upon periodic radiographic examination, which makes the marker processes subject to interval-censoring. A modified EM algorithm is used to deal with this incomplete data problem.
authors.affiliation: Department of Statistics and Actuarial Science, University of Waterloo, 200 University Avenue West Waterloo, Ontario, Canada N2L 3G1. b3chen@uwaterloo.ca
authors.forename: Eric Bingshu
authors.initials: EB
authors.lastname: Chen
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Cook
mesh_terms: D000465:Algorithms; D014408:Biomarkers, Tumor; D001859:Bone Neoplasms / Q000150:complications / Q000000981:diagnostic imaging / Q000556:secondary; D001943:Breast Neoplasms / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D003627:Data Interpretation, Statistical; D005260:Female; D006801:Humans; D009362:Neoplasm Metastasis; D011859:Radiography; D012008:Recurrence; D012044:Regression Analysis; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor