The nonparametric analysis of interval-censored failure time data

By interval-censored failure time data, we mean that the failure time of interest is observed to belong to some windows or intervals, instead of being known exactly. One would get an interval-censored observation for a survival event if a subject has not experienced the event at one follow-up time but had experienced the event at the next follow-up time. Interval-censored data include right-censored data (Kalbfleisch and Prentice, 2002) as a special case. Nonparametric comparison of survival functions is one of the main tasks in failure time studies such as clinical trials. For interval-censored failure time data, a few nonparametric test procedures have been developed. However, due to the strict restrictions of existing nonparametric tests and practical demands, some new nonparametric tests need to be developed. This dissertation consists of four parts. In the first part, we propose a new class of test procedures whose asymptotic distributions are established under both null and alternative hypotheses, since all of the existing test procedures cannot be used if one intends to perform some power or sample size calculation under the alternative hypothesis. Some numerical results have been obtained from a simulation study for assessing the finite sample performance of the proposed test procedure. Also we applied the proposed method to a real data set arising from an AIDS clinical trial concerning the opportunistic infection cytomegalovirus (CMV). The second part of this dissertation will focus on the nonparametric test for intervalcensored data with unequal censoring. As we know, one common drawback or restriction of the nonparametric test procedures given in the literature is that they can only apply to situations where the observation processes follow the same distribution among different treatment groups. To remove the restriction, a test procedure is proposed, which takes into account the difference between the distributions of the censoring variables. Also the asymptotic distribution of the test statistics i

Regression analysis of correlated interval-censored failure time data with a cured subgroup

Interval-censored failure time data commonly occur in many periodic follow-up studies such as epidemiological experiments, medical studies and clinical trials. By intervalcensored data, we usually mean that one cannot observe the failure time of interest and instead we know that it belongs to a time interval. Correlated failure time data commonly occur when there are multiple events on one individual or when the study subjects are clustered into some small groups. In this situation, study subjects from same subgroup or the failure events from same individuals are usually regarded as dependent, but the subjects in different clusters or failure events from different individuals are assumed to be independent. Besides the correlation between the cluster, sometimes the cluster size may be informative or carry some information about the failure time of interest. Cured subgroup is another interesting topic that has been discussed by many authors. For this situation, unlike the assumptions in traditional survival model that all study subjects would experience the failure event of interest eventually if the follow-up time is long enough, some subjects may never experience or not be susceptible to the event. Such subjects are treated as cured and assumed to belong to a cured subgroup in a study population. The research in this dissertation focuses on regression analysis of correlated intervalcensored data with a cured subgroup via different approaches based on different data structures. In the first part of this dissertation, we discuss clustered interval-censored data with a cured subgroup and informative cluster size. To address this, we present a within-cluster resampling method and in the approach, the multiple imputation procedure is applied for estimation of unknown parameters. To assess the performance of the proposed method, a simulation study is conducted and suggests that it works well in practical situations. Also, the method is applied to a set of real data that motivated this study. In the second part of this dissertation, we consider the clustered interval-censored data with a cured subgroup via a non-mixture cure model. We present a maximum likelihood estimation procedure under the semiparametric transformation nonmixture cure model. To estimate the unknown parameters, an expectation maximization (EM) algorithm based on an augmentation of Poisson variable is developed. To assess the performance of the proposed method, a simulation study is conducted and suggests that it works well in practical situations. An application to a study conducted by the National Aeronautics and Space Administration that motivated this study is also provided. In the third part of this dissertation, we investigate the bivariate interval-censored data with a cured subgroup. A sieve maximum likelihood estimation procedure under the semiparametric transformation non-mixture cure model based on Bernstein polynomials is presented. A simulation study is conducted to assess the finite sample performance of the proposed method and suggests that the proposed model works well. Also, a real data application from the study of AIDS Clinical Trial Group 181 is provided

Bayesian semiparametric inference for multivariate doubly-interval-censored data

Based on a data set obtained in a dental longitudinal study, conducted in Flanders (Belgium), the joint time to caries distribution of permanent first molars was modeled as a function of covariates. This involves an analysis of multivariate continuous doubly-interval-censored data since: (i) the emergence time of a tooth and the time it experiences caries were recorded yearly, and (ii) events on teeth of the same child are dependent. To model the joint distribution of the emergence times and the times to caries, we propose a dependent Bayesian semiparametric model. A major feature of the proposed approach is that survival curves can be estimated without imposing assumptions such as proportional hazards, additive hazards, proportional odds or accelerated failure time.Comment: Published in at http://dx.doi.org/10.1214/10-AOAS368 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

A semiparametric Bayesian proportional hazards model for interval censored data with frailty effects

<p>Abstract</p> <p>Background</p> <p>Multivariate analysis of interval censored event data based on classical likelihood methods is notoriously cumbersome. Likelihood inference for models which additionally include random effects are not available at all. Developed algorithms bear problems for practical users like: matrix inversion, slow convergence, no assessment of statistical uncertainty.</p> <p>Methods</p> <p>MCMC procedures combined with imputation are used to implement hierarchical models for interval censored data within a Bayesian framework.</p> <p>Results</p> <p>Two examples from clinical practice demonstrate the handling of clustered interval censored event times as well as multilayer random effects for inter-institutional quality assessment. The software developed is called survBayes and is freely available at CRAN.</p> <p>Conclusion</p> <p>The proposed software supports the solution of complex analyses in many fields of clinical epidemiology as well as health services research.</p

Modeling Arbitrarily Interval-Censored Survival Data with External Time-Dependent Covariates

Arbitrarily interval-censored survival data refer to the situation where the exact time of the occurrence of an event of interest is only known to have occurred within some two consecutive examinations. External time-dependent covariates refer to those whose values change during the periodic follow-up, and whose value at a particular time does not require individuals to be under direct observation. Regression modeling of survival data usually either handles arbitrarily interval-censored data alone (Farrington, 1996) or external time-dependent covariates alone (Cox, 1972; Therneau & Grambsch, 2000). In the current research, an adjustment has been made to the data augmentation used in Farrington’s estimation method for arbitrarily interval-censored data to accommodate external time-dependent covariates. The three approaches, regression analysis of arbitrarily interval-censored survival data by Farrington (1996), the extended Cox model (Cox, 1972; Therneau & Grambsch, 2000) for handling external time-dependent covariates, and the proposed model for handling both arbitrarily interval-censored data and external time-dependent covariates, were compared in terms of hypothesis testing performance. The simulation results revealed that the proposed model was more powerful than the other two models, and the type I error rate from the proposed model fluctuated around the nominal level .05, and was comparable to that from the extended Cox model. Moreover, the proposed model gave the smallest absolute relative bias of parameter estimates, and always gave the correct direction of the effect from the significant external time-dependent covariate. As such, the proposed model depicted the survival experience of subjects regarding the timing of the occurrence of an event more realistically. According to the results of the current research, the proposed model can be used in practice as an alternative to the popular extended Cox model (Cox, 1972; Therneau & Grambsch, 2000) for investigating what factors influence the survival times of subjects