2018•Pharmaceutical StatisticsOpen access

Tobit regression for modeling mean survival time using data subject to multiple sources of censoring

Qi Ming Gong, Douglas Earl Schaubel

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Abstract

Mean survival time is often of inherent interest in medical and epidemiologic studies. In the presence of censoring and when covariate effects are of interest, Cox regression is the strong default, but mostly due to convenience and familiarity. When survival times are uncensored, covariate effects can be estimated as differences in mean survival through linear regression. Tobit regression can validly be performed through maximum likelihood when the censoring times are fixed (ie, known for each subject, even in cases where the outcome is observed). However, Tobit regression is generally inapplicable when the response is subject to random right censoring. We propose Tobit regression methods based on weighted maximum likelihood which are applicable to survival times subject to both fixed and random censoring times. Under the proposed approach, known right censoring is handled naturally through the Tobit model, with inverse probability of censoring weighting used to overcome random censoring. Essentially, the re-weighting data are intended to represent those that would have been observed in the absence of random censoring. We develop methods for estimating the Tobit regression parameter, then the population mean survival time. A closed form large-sample variance estimator is proposed for the regression parameter estimator, with a semiparametric bootstrap standard error estimator derived for the population mean. The proposed methods are easily implementable using standard software. Finite-sample properties are assessed through simulation. The methods are applied to a large cohort of patients wait-listed for kidney transplantation.

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Mean survival time is often of inherent interest in medical and epidemiologic studies. In the presence of censoring and when covariate effects are of interest, Cox regression is the strong default, but mostly due to convenience and familiarity. When survival times are uncensored, covariate effects can be estimated as differences in mean survival through linear regression. Tobit regression can validly be performed through maximum likelihood when the censoring times are fixed (ie, known for each subject, even in cases where the outcome is observed). However, Tobit regression is generally inapplicable when the response is subject to random right censoring. We propose Tobit regression methods based on weighted maximum likelihood which are applicable to survival times subject to both fixed and random censoring times. Under the proposed approach, known right censoring is handled naturally through the Tobit model, with inverse probability of censoring weighting used to overcome random censoring. Essentially, the re-weighting data are intended to represent those that would have been observed in the absence of random censoring. We develop methods for estimating the Tobit regression parameter, then the population mean survival time. A closed form large-sample variance estimator is proposed for the regression parameter estimator, with a semiparametric bootstrap standard error estimator derived for the population mean. The proposed methods are easily implementable using standard software. Finite-sample properties are assessed through simulation. The methods are applied to a large cohort of patients wait-listed for kidney transplantation.

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Available abstract

Mean survival time is often of inherent interest in medical and epidemiologic studies. In the presence of censoring and when covariate effects are of interest, Cox regression is the strong default, but mostly due to convenience and familiarity. When survival times are uncensored, covariate effects can be estimated as differences in mean survival through linear regression. Tobit regression can validly be performed through maximum likelihood when the censoring times are fixed (ie, known for each subject, even in cases where the outcome is observed). However, Tobit regression is generally inapplicable when the response is subject to random right censoring. We propose Tobit regression methods based on weighted maximum likelihood which are applicable to survival times subject to both fixed and random censoring times. Under the proposed approach, known right censoring is handled naturally through the Tobit model, with inverse probability of censoring weighting used to overcome random censoring. Essentially, the re-weighting data are intended to represent those that would have been observed in the absence of random censoring. We develop methods for estimating the Tobit regression parameter, then the population mean survival time. A closed form large-sample variance estimator is proposed for the regression parameter estimator, with a semiparametric bootstrap standard error estimator derived for the population mean. The proposed methods are easily implementable using standard software. Finite-sample properties are assessed through simulation. The methods are applied to a large cohort of patients wait-listed for kidney transplantation.

Key concepts: Censoring (clinical trials), Tobit model, Statistics, Censored regression model, Covariate, Estimator, Mathematics, Proportional hazards model

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