Title: Design and analysis of nested case–control studies for recurrent events subject to a terminal event

Abstract

The process by which patients experience a series of recurrent events, such as hospitalizations, may be subject to death. In cohort studies, one strategy for analyzing such data is to fit a joint frailty model for the intensities of the recurrent event and death, which estimates covariate effects on the two event types while accounting for their dependence. When certain covariates are difficult to obtain, however, researchers may only have the resources to subsample patients on whom to collect complete data: one way is using the nested case–control (NCC) design, in which risk set sampling is performed based on a single outcome. We develop a general framework for the design of NCC studies in the presence of recurrent and terminal events and propose estimation and inference for a joint frailty model for recurrence and death using data arising from such studies. We propose a maximum weighted penalized likelihood approach using flexible spline models for the baseline intensity functions. Two standard error estimators are proposed: a sandwich estimator and a perturbation resampling procedure. We investigate operating characteristics of our estimators as well as design considerations via a simulation study and illustrate our methods using two studies: one on recurrent cardiac hospitalizationsmore » in patients with heart failure and the other on local recurrence and metastasis in patients with breast cancer.« less

Authors:

Jazić, Ina  ^[1];

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Haneuse, Sebastien ^[1]; French, Benjamin ^[2]; MacGrogan, Gaëtan ^[3]; Rondeau, Virginie ^[4]

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+ Show Author Affiliations

1. Department of Biostatistics Harvard T.H. Chan School of Public Health Boston Massachusetts
2. Department of Statistics Radiation Effects Research Foundation Hiroshima Japan
3. Department of Biopathology Institut Bergonié Bordeaux France
4. Centre de recherche INSERM U1219 Université de Bordeaux–ISPED Bordeaux France

Publication Date:

Tue Jul 09 00:00:00 EDT 2019

Sponsoring Org.:

USDOE

OSTI Identifier:

1532770

Grant/Contract Number:  

DE‐HS0000031

Resource Type:

Publisher's Accepted Manuscript

Journal Name:

Statistics in Medicine

Additional Journal Information:

Journal Name: Statistics in Medicine Journal Volume: 38 Journal Issue: 22; Journal ID: ISSN 0277-6715

Publisher:

Wiley Blackwell (John Wiley & Sons)

Country of Publication:

United Kingdom

Language:

English