On estimands arising from misspecified semiparametric rate-based analysis of recurrent episodic conditions
Loading...
Date
2019-11-10
Authors
Lee, Jooyoung
Cook, Richard J.
Journal Title
Journal ISSN
Volume Title
Publisher
Wiley
Abstract
Marginal rate-based analyses are widely used for the analysis of recurrent events in clinical trials. In many areas of application, the events are not instantaneous but rather signal the onset of a symptomatic episode representing a recurrent infection, respiratory exacerbation, or bout of acute depression. In rate-based analyses, it is unclear how to best handle the time during which individuals are experiencing symptoms and hence are not at risk. We derive the limiting value of theNelson-Aalen estimator and estimators of the regression coefficients under a semiparametric rate-based model in terms of an underlying two-state process. We investigate the impact of the distribution of the episode durations, heterogeneity, and dependence on the asymptotic and finite sample properties of standard estimators. We also consider the impact of these features on power in trials designed to test intervention effects on rate functions. An application to a trial of individuals with herpes simplex virus is given for illustration.
Description
This is the peer reviewed version of the following article: Jooyoung Lee and Richard J. Cook. On estimands arising from misspecified semiparametric rate-based analysis of recurrent episodic conditions. Statistics in Medicine (2019), 38 (25): 4977–4998 which has been published in final form at https://doi.org/10.1002/sim.8345.This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
Keywords
estimands, heterogeneity, intensity function, misspecification, rate function, recurrent episodes