Recurrent event time data and more general multiple event time data are commonly analyzed using extensions of Cox regression, or proportional hazards regression, as used with single event time data. These methods trea...Recurrent event time data and more general multiple event time data are commonly analyzed using extensions of Cox regression, or proportional hazards regression, as used with single event time data. These methods treat covariates, either time-invariant or time-varying, as having multiplicative effects while general dependence on time is left un-estimated. An adaptive approach is formulated for analyzing multiple event time data. Conditional hazard rates are modeled in terms of dependence on both time and covariates using fractional polynomials restricted so that the conditional hazard rates are positive-valued and so that excess time probability functions (generalizing survival functions for single event times) are decreasing. Maximum likelihood is used to estimate parameters adjusting for right censored event times. Likelihood cross-validation (LCV) scores are used to compare models. Adaptive searches through alternate conditional hazard rate models are controlled by LCV scores combined with tolerance parameters. These searches identify effective models for the underlying multiple event time data. Conditional hazard regression is demonstrated using data on times between tumor recurrence for bladder cancer patients. Analyses of theory-based models for these data using extensions of Cox regression provide conflicting results on effects to treatment group and the initial number of tumors. On the other hand, fractional polynomial analyses of these theory-based models provide consistent results identifying significant effects to treatment group and initial number of tumors using both model-based and robust empirical tests. Adaptive analyses further identify distinct moderation by group of the effect of tumor order and an additive effect to group after controlling for nonlinear effects to initial number of tumors and tumor order. Results of example analyses indicate that adaptive conditional hazard rate modeling can generate useful insights into multiple event time data.展开更多
Recurrent event time data and more general multiple event time data are commonly analyzed using extensions of Cox regression, or proportional hazards regression, as used with single event time data. These methods trea...Recurrent event time data and more general multiple event time data are commonly analyzed using extensions of Cox regression, or proportional hazards regression, as used with single event time data. These methods treat covariates, either time-invariant or time-varying, as having multiplicative effects while general dependence on time is left un-estimated. An adaptive approach is formulated for analyzing multiple event time data. Conditional hazard rates are modeled in terms of dependence on both time and covariates using fractional polynomials restricted so that the conditional hazard rates are positive-valued and so that excess time probability functions (generalizing survival functions for single event times) are decreasing. Maximum likelihood is used to estimate parameters adjusting for right censored event times. Likelihood cross-validation (LCV) scores are used to compare models. Adaptive searches through alternate conditional hazard rate models are controlled by LCV scores combined with tolerance parameters. These searches identify effective models for the underlying multiple event time data. Conditional hazard regression is demonstrated using data on times between tumor recurrence for bladder cancer patients. Analyses of theory-based models for these data using extensions of Cox regression provide conflicting results on effects to treatment group and the initial number of tumors. On the other hand, fractional polynomial analyses of these theory-based models provide consistent results identifying significant effects to treatment group and initial number of tumors using both model-based and robust empirical tests. Adaptive analyses further identify distinct moderation by group of the effect of tumor order and an additive effect to group after controlling for nonlinear effects to initial number of tumors and tumor order. Results of example analyses indicate that adaptive conditional hazard rate modeling can generate useful insights into multiple event time data.展开更多
Recurrent event gap times data frequently arise in biomedical studies and often more than one type of event is of interest. To evaluate the effects of covariates on the marginal recurrent event hazards functions, ther...Recurrent event gap times data frequently arise in biomedical studies and often more than one type of event is of interest. To evaluate the effects of covariates on the marginal recurrent event hazards functions, there exist two types of hazards models： the multiplicative hazards model and the additive hazards model. In the paper, we propose a more flexible additive-multiplicative hazards model for multiple type of recurrent gap times data, wherein some covariates are assumed to be additive while others are multiplicative. An estimating equation approach is presented to estimate the regression parameters. We establish asymptotic properties of the proposed estimators.展开更多
Recurrent events data and gap times between recurrent events are frequently encountered in many clinical and observational studies,and often more than one type of recurrent events is of interest.In this paper,we consi...Recurrent events data and gap times between recurrent events are frequently encountered in many clinical and observational studies,and often more than one type of recurrent events is of interest.In this paper,we consider a proportional hazards model for multiple type recurrent gap times data to assess the effect of covaxiates on the censored event processes of interest.An estimating equation approach is used to obtain the estimators of regression coefficients and baseline cumulative hazard functions.We examine asymptotic properties of the proposed estimators.Finite sample properties of these estimators are demonstrated by simulations.展开更多
文摘Recurrent event time data and more general multiple event time data are commonly analyzed using extensions of Cox regression, or proportional hazards regression, as used with single event time data. These methods treat covariates, either time-invariant or time-varying, as having multiplicative effects while general dependence on time is left un-estimated. An adaptive approach is formulated for analyzing multiple event time data. Conditional hazard rates are modeled in terms of dependence on both time and covariates using fractional polynomials restricted so that the conditional hazard rates are positive-valued and so that excess time probability functions (generalizing survival functions for single event times) are decreasing. Maximum likelihood is used to estimate parameters adjusting for right censored event times. Likelihood cross-validation (LCV) scores are used to compare models. Adaptive searches through alternate conditional hazard rate models are controlled by LCV scores combined with tolerance parameters. These searches identify effective models for the underlying multiple event time data. Conditional hazard regression is demonstrated using data on times between tumor recurrence for bladder cancer patients. Analyses of theory-based models for these data using extensions of Cox regression provide conflicting results on effects to treatment group and the initial number of tumors. On the other hand, fractional polynomial analyses of these theory-based models provide consistent results identifying significant effects to treatment group and initial number of tumors using both model-based and robust empirical tests. Adaptive analyses further identify distinct moderation by group of the effect of tumor order and an additive effect to group after controlling for nonlinear effects to initial number of tumors and tumor order. Results of example analyses indicate that adaptive conditional hazard rate modeling can generate useful insights into multiple event time data.
文摘Recurrent event time data and more general multiple event time data are commonly analyzed using extensions of Cox regression, or proportional hazards regression, as used with single event time data. These methods treat covariates, either time-invariant or time-varying, as having multiplicative effects while general dependence on time is left un-estimated. An adaptive approach is formulated for analyzing multiple event time data. Conditional hazard rates are modeled in terms of dependence on both time and covariates using fractional polynomials restricted so that the conditional hazard rates are positive-valued and so that excess time probability functions (generalizing survival functions for single event times) are decreasing. Maximum likelihood is used to estimate parameters adjusting for right censored event times. Likelihood cross-validation (LCV) scores are used to compare models. Adaptive searches through alternate conditional hazard rate models are controlled by LCV scores combined with tolerance parameters. These searches identify effective models for the underlying multiple event time data. Conditional hazard regression is demonstrated using data on times between tumor recurrence for bladder cancer patients. Analyses of theory-based models for these data using extensions of Cox regression provide conflicting results on effects to treatment group and the initial number of tumors. On the other hand, fractional polynomial analyses of these theory-based models provide consistent results identifying significant effects to treatment group and initial number of tumors using both model-based and robust empirical tests. Adaptive analyses further identify distinct moderation by group of the effect of tumor order and an additive effect to group after controlling for nonlinear effects to initial number of tumors and tumor order. Results of example analyses indicate that adaptive conditional hazard rate modeling can generate useful insights into multiple event time data.
基金The Science Foundation(JA12301)of Fujian Educational Committeethe Teaching Quality Project(ZL0902/TZ(SJ))of Higher Education in Fujian Provincial Education Department
文摘Recurrent event gap times data frequently arise in biomedical studies and often more than one type of event is of interest. To evaluate the effects of covariates on the marginal recurrent event hazards functions, there exist two types of hazards models： the multiplicative hazards model and the additive hazards model. In the paper, we propose a more flexible additive-multiplicative hazards model for multiple type of recurrent gap times data, wherein some covariates are assumed to be additive while others are multiplicative. An estimating equation approach is presented to estimate the regression parameters. We establish asymptotic properties of the proposed estimators.
基金supported in part by Natural Science Foundation of Hubei(08BA164)Major Research Program of Hubei Provincial Department of Education(09B2001)+2 种基金supported in part by National Natural Science Foundation of China(1117112)Doctoral Fund of Ministry of Education of China(20090076110001)National Statistical Science Research Major Program of China(2011LZ051)
文摘Recurrent events data and gap times between recurrent events are frequently encountered in many clinical and observational studies,and often more than one type of recurrent events is of interest.In this paper,we consider a proportional hazards model for multiple type recurrent gap times data to assess the effect of covaxiates on the censored event processes of interest.An estimating equation approach is used to obtain the estimators of regression coefficients and baseline cumulative hazard functions.We examine asymptotic properties of the proposed estimators.Finite sample properties of these estimators are demonstrated by simulations.
