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Shared frailty models are of interest when one has clustered survival data and when focus is on comparing the lifetimes within clusters and further on estimating the correlation between lifetimes from the same cluster. It is well known that the positive stable model should be preferred to the gamma model in situations where the correlated survival data show a decreasing association with time. In this paper, we devise a likelihood based estimation procedure for the positive stable shared frailty Cox model, which is expected to obtain high efficiency. The proposed estimator is provided with large sample properties and also a consistent estimator of standard errors is given. Simulation studies show that the estimation procedure is appropriate for practical use, and that it is much more efficient than a recently suggested procedure. The suggested methodology is applied to a dataset concerning time to blindness for patients with diabetic retinopathy.

It is of interest in some applications to determine whether there is a relationship between a hazard rate function (or a cumulative incidence function) and a mark variable which is only observed at uncensored failure times. We develop nonparametric tests for this problem when the mark variable is continuous. Tests are developed for the null hypothesis that the mark-specific hazard rate is independent of the mark versus ordered and two-sided alternatives expressed in terms of mark-specific hazard functions and mark-specific cumulative incidence functions. The test statistics are based on functionals of a bivariate test process equal to a weighted average of differences between a Nelson–Aalen-type estimator of the mark-specific cumulative hazard function and a nonparametric estimator of this function under the null hypothesis. The weight function in the test process can be chosen so that the test statistics are asymptotically distribution-free. Asymptotically correct critical values are obtained through a simple simulation procedure. The testing procedures are shown to perform well in numerical studies, and are illustrated with an AIDS clinical trial example. Specifically, the tests are used to assess if the instantaneous or absolute risk of treatment failure depends on the amount of accumulation of drug resistance mutations in a subject's HIV virus. This assessment helps guide development of anti-HIV therapies that surmount the problem of drug resistance.

This paper presents a semi-parametric modeling technique for estimating the survival function from a set of right-censored time-to-event data. Our method, named pseudo-value regression trees (PRT), is based on the pseudo-value regression framework, modeling individual-specific survival probabilities by computing pseudo-values and relating them to a set of covariates. The standard approach to pseudo-value regression is to fit a main-effects model using generalized estimating equations (GEE). PRT extend this approach by building a multivariate regression tree with pseudo-value outcome and by successively fitting a set of regularized additive models to the data in the nodes of the tree. Due to the combination of tree learning and additive modeling, PRT are able to perform variable selection and to identify relevant interactions between the covariates, thereby addressing several limitations of the standard GEE approach. In addition, PRT include time-dependent effects in the node-wise models. Interpretability of the PRT fits is ensured by controlling the tree depth. Based on the results of two simulation studies, we investigate the properties of the PRT method and compare it to several alternative modeling techniques. Furthermore, we illustrate PRT by analyzing survival in 3,652 patients enrolled for a randomized study on primary invasive breast cancer.

Consider lifetimes originating at a series of calendar times $$ t_{1} ,t_{2} , \ldots $$ . At a certain time $$ t_{0} $$ a cross-sectional sample is taken, generating a sample of current durations (backward recurrence times) of survivors until $$ t_{0} $$ and a prevalent cohort study consisting of survival times left-truncated at the current durations. A Lexis diagram is helpful in visualizing this situation. Survival analysis based on current durations and prevalent cohort studies is now well-established as long as all covariates are observed. The general problems with unobserved covariates have been well understood for ordinary prospective follow-up studies, with the good help of hazard rate models incorporating frailties: as for ordinary regression models, the added noise generates attenuation in the regression parameter estimates. For prevalent cohort studies this attenuation remains, but in addition one needs to take account of the differential selection of the survivors from initiation $$ t_{i} $$ to cross-sectional sampling at $$ t_{0} $$ . This paper intends to survey the recent development of these matters and the consequences for routine use of hazard rate models or accelerated failure time models in the many cases where unobserved heterogeneity may be an issue. The study was inspired by concrete problems in the study of time-to-pregnancy, and we present various simulation results inspired by this particular application.

Incomplete covariate data is a common occurrence in many studies in which the outcome is survival time. With generalized linear models, when the missing covariates are categorical, a useful technique for obtaining parameter estimates is the EM by the method of weights proposed in Ibrahim (1990). In this article, we extend the EM by the method of weights to survival outcomes whose distributions may not fall in the class of generalized linear models. This method requires the estimation of the parameters of the distribution of the covariates. We present a clinical trials example with five covariates, four of which have some missing values.

The recurrent/terminal event data structure has undergone considerable methodological development in the last 10–15 years. An example of the data structure that has arisen with increasing frequency involves the recurrent event being hospitalization and the terminal event being death. We consider the response Survival-Out-of-Hospital, defined as a temporal process (indicator function) taking the value 1 when the subject is currently alive and not hospitalized, and 0 otherwise. Survival-Out-of-Hospital is a useful alternative strategy for the analysis of hospitalization/survival in the chronic disease setting, with the response variate representing a refinement to survival time through the incorporation of an objective quality-of-life component. The semiparametric model we consider assumes multiplicative covariate effects and leaves unspecified the baseline probability of being alive-and-out-of-hospital. Using zero-mean estimating equations, the proposed regression parameter estimator can be computed without estimating the unspecified baseline probability process, although baseline probabilities can subsequently be estimated for any time point within the support of the censoring distribution. We demonstrate that the regression parameter estimator is asymptotically normal, and that the baseline probability function estimator converges to a Gaussian process. Simulation studies are performed to show that our estimating procedures have satisfactory finite sample performances. The proposed methods are applied to the Dialysis Outcomes and Practice Patterns Study (DOPPS), an international end-stage renal disease study.

In the model of type I censored exponential lifetimes, coverage probabilities are compared for a number of confidence interval constructions proposed in literature. The coverage probabilities are calculated exactly for sample sizes up to 50 and for different degrees of censoring and different degrees of intended confidence. If not only a fair two-sided coverage is desired, but also fair one-sided coverage's, only few methods are quite satisfactory. A likelihood-based interval and a third root transformation to normality work almost perfectly, but the χ2-based method that is perfect under no censoring and under type II censoring can also be advocated.

A method for estimating the dependence of intrinsic intervention benefits on time elapsed since the intervention took place is proposed. The method is aimed at intervention programs against diseases where one or all of the following components of hazard intensity may undergo important and unknown variations: 1) the intervention benefits to a subject are a function of the time elapsed since the intervention took place, or since inception for a continuing treatment, 2) the subjects vulnerability is an unknown function of their age, 3) the exogenous or environmental baseline intensity, to which all are assumed subjected, fluctuates arbitrarily with calendar time. During the time span of a study, these variables interact in a complex way, possibly masking the real contribution of the intervention. However, with very general assumptions about how hazard components interact, the cumulative hazards of subpopulations treated at different times in the past are shown to be described mathematically by a convolution of the time elapsed dependent intervention benefit function with the age and calendar time dependent baseline intensity. Starting from the cumulative hazards of untreated and treated subpopulations that had the intervention at different times in the past, a method of deconvolution through regularization is proposed to reconstruct the time elapsed dependence of the intervention benefit function. The regularization technique used is of the ‘penalized least square smoothing’ type, it is applied to the solution of Volterra integral equations of the first kind under noisy inputs. Simulations, to test for the reconstruction of different modes of time elapsed variation of the intervention benefits, are carried out on realistically noisy ‘data sets’ taken to be available at a limited number of time points. The stability of the estimated reconstructions, to measurement errors, is examined through repeated simulations with random noise added to inputs. The method is applied to a Brazilian data set where BCG vaccination resulted in a small reduction in the cumulated risk of leprosy infection.

This paper proposes a new treatment for electrical insulation degradation. Some types of insulation which have been used under various circumstances are considered to degrade at various rates in accordance with their stress circumstances. The cross-linked polyethylene (XLPE) insulated cables inspected by major Japanese electric companies clearly indicate such phenomena. By assuming that the inspected specimen is sampled from one of the clustered groups, a mixed degradation model can be constructed. Since the degradation of the insulation under common circumstances is considered to follow a Weibull distribution, a mixture model and a Weibull power law can be combined. This is called The mixture Weibull power law model. By using the maximum likelihood estimation for the newly proposed model to Japanese 22 and 33kV insulation class cables, they are clustered into a certain number of groups by using the AIC and the generalized likelihood ratio test method. The reliability of the cables at specified years are assessed.