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Informative censoring in survival analysis and application to asthma
Abstract
In epidemiological studies, survival analyses are often carried out in order to better understand the onset of an event. The data have the particularity of being incomplete due to the different censoring phenomena. Traditional methods make the hypothesis of censoring being independent from the event, which may be a source of bias in certain pathologies. The Inverse Probability of Censoring Weighted (IPCW) method adapts the Kaplan-Meier estimators and the Cox partial likelihood method to cases, with non-independent censoring. This method uses the information resulting from censoring to modify the contribution of individuals in the estimators. This method is applied to asthma, a case in which therapists believe that patients lost to follow-up are patients who are in otherwise good health, and do not feel the necessity to consult a doctor (informative censoring).
... Une première partie présente la méthode IPCW pour modèles de survie. Cette partie reprend essentiellement les résultats d'un article (Saint-Pierre et al. [2005b]) soumis dans la revue Biometrical Journal. Elle est inspirée des travaux de Castelli [2004] et de Robins et Finkelstein [2000]. ...
... Les méthodes d'estimation présentées dans le cadre du modèle Markov non-homogène (et du modèle semi-Markovien) supposent que le mécanisme de censure n'apporte aucune information sur l'évolution de la maladie. Cette hypothèse étant rarement vérifiée en pratique, nous présentons une méthode d'estimation permettant de prendre en compte une censure informative dans l'étude de la survie (Saint-Pierre et al. [2005b]). En s'inspirant des méthodes d'estimation dans un modèle de Markov non-homogène, nous avons étendu 147 cette méthodologie au cas des modèles progressifs et des modèles Markoviens à deux états réversibles où la censure pose les mêmes difficultés. ...
Gilles DUCHARME (président du jury)
Catherine HUBER (rapporteur)
Gérard TAP (examinateur)
Abdelkader EL HASNAOUI (examinateur)
Michel AUBIER (rapporteur)
... The exclusion of censoring assumption from different studies may generally lead to biased estimates. Castelli et al. [10] in adapting the Inverse Probability of Censoring Weighted [IPCW] to study the survival times of asthma patients while including informative censoring [patients felt they were okay and did not need to consult a doctor] show that information coming from censoring process improves the survival estimate. Another approach is that by Ghosh et al., [9] where they introduce a semi-parametric approach for recurrent events in the presence of dependent censoring and apply it ALIVE cohort study. ...
In this study, we adapt a Cox-based model for recurrent events; the Prentice, Williams and Peterson Total-Time (PWP-TT) that has largely, been used under the assumption of non-informative censoring and evaluate it under an informative censoring setting. Empirical evaluation was undertaken with the aid of the semi-parametric framework for recurrent events suggested by Huang [1] and implemented in R Studio software. For validation we used data from a typical HIV care setting in Kenya. Of the three models under consideration; the standard Cox Model had gender hazard ratio (HR) of 0.66 (p-value=0.165), Andersen-Gill had HR 0.46 (with borderline p-value=0.054) and extended PWP TT had HR 0.22 (p-value=0.006). The PWP-TT model performed better as compared to other models under informative setting. In terms of risk factors under informative setting, LTFU due to stigma; gender [base=Male] had HR 0.544 (p-value =0.002), age [base is < 37] had HR 0.772 (p-value=0.008), ART regimen [base= First line] had HR 0.518 (p-value= 0.233) and differentiated care model (Base=not on DCM) had HR 0.77(p-value=0.036). In conclusion, in spite of the multiple interventions designed to address incidences of LTFU among HIV patients, within-person cases of LTFU are usually common and recurrent in nature, with the present likelihood of a person getting LTFU influenced by previous occurrences and therefore informative censoring should be checked.
An adaptive two stage allocation design is developed for survival responses subject to independent informative censoring. Asymptotic p value of a score test related to a hypothesis of treatment effectiveness is used to set the assignment probability of the second stage. Several characteristics of the design and the follow-up inference are studied, both numerically and theoretically, and are compared with those of an existing competitor. Applicability of the proposed design is also illustrated through a real data.
A multi-treatment two stage adaptive allocation design is developed for survival responses. Assuming noninformative random censoring, asymptotic p values of relevant tests of equality of treatment effects are used to derive the assignment probability of incoming second stage subjects. Several ethical and inferential criteria of the design are studied, and are compared with those of an existing competitor. Applicability and performance of the proposed design are also illustrated using a data arising from a real clinical trial.
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